Skip to main content

Advertisement

SpringerLink
Log in

Prognostic Value of Programmed Death Ligand-1 Expression in Solid Tumors Irrespective of Immunotherapy Exposure: A Systematic Review and Meta-Analysis

  • Systematic Review
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Background

The programmed cell death-1/programmed cell death ligand-1 (PD-L1) pathway, which plays a crucial role in cancer immune surveillance, is the target of several approved immunotherapeutic agents and is used as a predictive biomarker in some solid tumors. However, its use as a prognostic marker (i.e., regardless of therapy used) is not established clearly with available data demonstrating inconsistent prognostic impact of PD-L1 expression in solid tumors.

Methods

We conducted a systematic literature search of electronic databases and identified publications exploring the effect of PD-L1 expression on overall survival and/or disease-free survival. Hazard ratios were pooled in a meta-analysis using generic inverse-variance and random-effects modeling. We used the Deeks method to explore subgroup differences based on disease site, stage of disease, and method of PD-L1 quantification.

Results

One hundred and eighty-six studies met the inclusion criteria. Programmed cell death ligand-1 expression was associated with worse overall survival (hazard ratio 1.33, 95% confidence interval 1.26–1.39; p < 0.001). There was significant heterogeneity between disease sites (subgroup p = 0.002) with pancreatic, hepatocellular, and genitourinary cancers associated with the highest magnitude of adverse outcomes. Programmed cell death ligand-1 was also associated with worse overall disease-free survival (hazard ratio 1.19, 95% confidence interval 1.09–1.30; p < 0.001). Stage of disease did not significantly affect the results (subgroup p = 0.52), nor did the method of quantification via immunohistochemistry or messenger RNA (subgroup p = 0.70).

Conclusions

High expression of PD-L1 is associated with worse survival in solid tumors albeit with significant heterogeneity among tumor types. The effect is consistent in early-stage and metastatic disease and is not sensitive to method of PD-L1 quantification. These data can provide additional information for the counseling of patients with cancer about prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14(10):1014–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Keenan TE, Burke KP, Van Allen EM. Genomic correlates of response to immune checkpoint blockade. Nat Med. 2019;25(3):389–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Walunas TL, Lenschow DJ, Bakker CY, et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994;1(5):405–13.

    Article  CAS  PubMed  Google Scholar 

  5. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002;99(19):12293–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7–H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.

    Article  CAS  PubMed  Google Scholar 

  7. Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67–76.

    Article  CAS  PubMed  Google Scholar 

  8. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.

    Article  PubMed  Google Scholar 

  9. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50.

    Article  CAS  PubMed  Google Scholar 

  10. Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019;393(10189):2404–15.

    Article  PubMed  Google Scholar 

  11. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108–21.

    Article  CAS  PubMed  Google Scholar 

  12. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint. Immunity. 2018;48(3):434–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lee SJ, Jang BC, Lee SW, et al. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7–H1 (CD274). FEBS Lett. 2006;580(3):755–62.

    Article  CAS  PubMed  Google Scholar 

  15. Blank C, Gajewski TF, Mackensen A. Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy. Cancer Immunol Immunother. 2005;54(4):307–14.

    Article  CAS  PubMed  Google Scholar 

  16. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wu Y, Chen W, Xu ZP, Gu W. PD-L1 Distribution and perspective for cancer immunotherapy-blockade, knockdown, or inhibition. Front Immunol. 2019;10:2022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang X, Teng F, Kong L, Yu J. PD-L1 expression in human cancers and its association with clinical outcomes. Onco Targets Ther. 2016;9:5023–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kingwell K. Neuro-oncology: glioblastoma prognosis linked to neuronal PD-L1 expression in tumour-adjacent tissue. Nat Rev Neurol. 2013;9(11):602–3.

    Article  PubMed  Google Scholar 

  20. Kan G, Dong W. The expression of PD-L1 APE1 and P53 in hepatocellular carcinoma and its relationship to clinical pathology. Eur Rev Med Pharmacol Sci. 2015;19(16):3063–71.

    CAS  PubMed  Google Scholar 

  21. Lote H, Cafferkey C, Chau I. PD-1 and PD-L1 blockade in gastrointestinal malignancies. Cancer Treat Rev. 2015;41(10):893–903.

    Article  CAS  PubMed  Google Scholar 

  22. Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med. 2015;21(1):24–33.

    Article  CAS  PubMed  Google Scholar 

  23. Darb-Esfahani S, Kunze CA, Kulbe H, et al. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma. Oncotarget. 2016;7(2):1486–99.

    Article  PubMed  Google Scholar 

  24. Sacher AG, Gandhi L. Biomarkers for the clinical use of PD-1/PD-L1 inhibitors in non-small-cell lung cancer: a review. JAMA Oncol. 2016;2(9):1217–22.

    Article  PubMed  Google Scholar 

  25. Udall M, Rizzo M, Kenny J, et al. PD-L1 diagnostic tests: a systematic literature review of scoring algorithms and test-validation metrics. Diagn Pathol. 2018;13(1):12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Shklovskaya E, Rizos H. Spatial and temporal changes in PD-L1 expression in cancer: the role of genetic drivers, tumor microenvironment and resistance to therapy. Int J Mol Sci. 2020;21(19):7139.

    Article  CAS  PubMed Central  Google Scholar 

  27. Vilain RE, Menzies AM, Wilmott JS, et al. Dynamic changes in PD-L1 expression and immune infiltrates early during treatment predict response to PD-1 blockade in melanoma. Clin Cancer Res. 2017;23(17):5024–33.

    Article  CAS  PubMed  Google Scholar 

  28. Davis AA, Patel VG. The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. J Immunother Cancer. 2019;7(1):278.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Oldenhuis CN, Oosting SF, Gietema JA, de Vries EG. Prognostic versus predictive value of biomarkers in oncology. Eur J Cancer. 2008;44(7):946–53.

    Article  CAS  PubMed  Google Scholar 

  30. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.

    Article  PubMed  PubMed Central  Google Scholar 

  31. HIRU HIRU. Search strategies for MEDLINE in Ovid Syntax and the PubMed translation. https://hiru.mcmaster.ca/hiru/HIRU_Hedges_MEDLINE_Strategies.aspx#Prognosis. Accessed 12 Apr 2021.

  32. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17(24):2815–34.

    Article  CAS  PubMed  Google Scholar 

  33. Deeks JJ. Systematic reviews in health care: systematic reviews of evaluations of diagnostic and screening tests. BMJ. 2001;323(7305):157–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Stanley TD, Doucouliagos H. Neither fixed nor random: weighted least squares meta-regression. Res Synth Methods. 2017;8(1):19–42.

    Article  CAS  PubMed  Google Scholar 

  35. Ameratunga M, Asadi K, Lin X, et al. PD-L1 and tumor infiltrating lymphocytes as prognostic markers in resected NSCLC. PLoS ONE. 2016;11(4):e0153954.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Bayram S, Akkiz H, Ulger Y, Bekar A, Akgollu E, Yildirim S. Lack of an association of programmed cell death-1 PD1.3 polymorphism with risk of hepatocellular carcinoma susceptibility in Turkish population: a case-control study. Gene. 2012;511(2):308–13.

    Article  CAS  PubMed  Google Scholar 

  37. Behr DS, Peitsch WK, Hametner C, et al. Prognostic value of immune cell infiltration, tertiary lymphoid structures and PD-L1 expression in Merkel cell carcinomas. Int J Clin Exp Pathol. 2014;7(11):7610–21.

    PubMed  PubMed Central  Google Scholar 

  38. Boger C, Behrens HM, Mathiak M, Kruger S, Kalthoff H, Rocken C. PD-L1 is an independent prognostic predictor in gastric cancer of Western patients. Oncotarget. 2016;7(17):24269–83.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Boland JM, Kwon ED, Harrington SM, et al. Tumor B7–H1 and B7–H3 expression in squamous cell carcinoma of the lung. Clin Lung Cancer. 2013;14(2):157–63.

    Article  CAS  PubMed  Google Scholar 

  40. Chang H, Jung W, Kim A, et al. Expression and prognostic significance of programmed death protein 1 and programmed death ligand-1, and cytotoxic T lymphocyte-associated molecule-4 in hepatocellular carcinoma. APMIS. 2017;125(8):690–8.

    Article  CAS  PubMed  Google Scholar 

  41. Chang YL, Yang CY, Huang YL, Wu CT, Yang PC. High PD-L1 expression is associated with stage IV disease and poorer overall survival in 186 cases of small cell lung cancers. Oncotarget. 2017;8(11):18021–30.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Chen Y, Zhang Y, Chai X, et al. Correlation between the expression of PD-L1 and clinicopathological features in patients with thymic epithelial tumors. BioMed Res Int. 2018;2018:5830547.

    PubMed  PubMed Central  Google Scholar 

  43. Cho J, Ahn S, Yoo KH, et al. Treatment outcome of PD-1 immune checkpoint inhibitor in Asian metastatic melanoma patients: correlative analysis with PD-L1 immunohistochemistry. Invest New Drugs. 2016;34(6):677–84.

    Article  CAS  PubMed  Google Scholar 

  44. Choueiri TK, Figueroa DJ, Fay AP, et al. Correlation of PD-L1 tumor expression and treatment outcomes in patients with renal cell carcinoma receiving sunitinib or pazopanib: results from COMPARZ, a randomized controlled trial. Clin Cancer Res. 2015;21(5):1071–7.

    Article  CAS  PubMed  Google Scholar 

  45. Chovanec M, Cierna Z, Miskovska V, et al. Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors. Oncotarget. 2017;8(13):21794–805.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Danilova L, Wang H, Sunshine J, et al. Association of PD-1/PD-L axis expression with cytolytic activity, mutational load, and prognosis in melanoma and other solid tumors. Proc Natl Acad Sci U S A. 2016;113(48):E7769–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. De Meulenaere A, Vermassen T, Aspeslagh S, et al. Tumor PD-L1 status and CD8(+) tumor-infiltrating T cells: markers of improved prognosis in oropharyngeal cancer. Oncotarget. 2017;8(46):80443–52.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Diana A, Wang LM, D’Costa Z, et al. Prognostic value, localization and correlation of PD-1/PD-L1, CD8 and FOXP3 with the desmoplastic stroma in pancreatic ductal adenocarcinoma. Oncotarget. 2016;7(27):40992–1004.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Driver BR, Miller RA, Miller T, et al. Programmed death ligand-1 (PD-L1) expression in either tumor cells or tumor-infiltrating immune cells correlates with solid and high-grade lung adenocarcinomas. Arch Pathol Lab Med. 2017;141(11):1529–32.

    Article  CAS  PubMed  Google Scholar 

  50. Gevensleben H, Holmes EE, Goltz D, et al. PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy. Oncotarget. 2016;7(48):79943–55.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Goltz D, Holmes EE, Gevensleben H, et al. CXCL12 promoter methylation and PD-L1 expression as prognostic biomarkers in prostate cancer patients. Oncotarget. 2016;7(33):53309–20.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Guan J, Lim KS, Mekhail T, Chang CC. Programmed death ligand-1 (PD-L1) expression in the programmed death receptor-1 (PD-1)/PD-L1 blockade: a key player against various cancers. Arch Pathol Lab Med. 2017;141(6):851–61.

    Article  CAS  PubMed  Google Scholar 

  53. Haratake N, Toyokawa G, Takada K, et al. Programmed death-ligand 1 expression and EGFR mutations in multifocal lung cancer. Ann Thorac Surg. 2018;105(2):448–54.

    Article  PubMed  Google Scholar 

  54. Harter PN, Bernatz S, Scholz A, et al. Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases. Oncotarget. 2015;6(38):40836–49.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hirai M, Kitahara H, Kobayashi Y, et al. Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment. Int J Oncol. 2017;50(1):41–8.

    Article  CAS  PubMed  Google Scholar 

  57. Inaguma S, Lasota J, Wang Z, Felisiak-Golabek A, Ikeda H, Miettinen M. Clinicopathologic profile, immunophenotype, and genotype of CD274 (PD-L1)-positive colorectal carcinomas. Mod Pathol. 2017;30(2):278–85.

    Article  CAS  PubMed  Google Scholar 

  58. Jiang C, Yuan F, Wang J, Wu L. Oral squamous cell carcinoma suppressed antitumor immunity through induction of PD-L1 expression on tumor-associated macrophages. Immunobiology. 2017;222(4):651–7.

    Article  CAS  PubMed  Google Scholar 

  59. Jie HB, Srivastava RM, Argiris A, Bauman JE, Kane LP, Ferris RL. Increased PD-1+ and TIM-3+ TILs during cetuximab therapy inversely correlate with response in head and neck cancer patients. Cancer Immunol Res. 2017;5(5):408–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kakavand H, Vilain RE, Wilmott JS, et al. Tumor PD-L1 expression, immune cell correlates and PD-1+ lymphocytes in sentinel lymph node melanoma metastases. Mod Pathol. 2015;28(12):1535–44.

    Article  CAS  PubMed  Google Scholar 

  61. Kamphorst AO, Pillai RN, Yang S, et al. Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1-targeted therapy in lung cancer patients. Proc Natl Acad Sci U S A. 2017;114(19):4993–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kansy BA, Concha-Benavente F, Srivastava RM, et al. PD-1 status in CD8+ T cells associates with survival and anti-PD-1 therapeutic outcomes in head and neck cancer. Cancer Res. 2017;77(22):6353–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kerr KM, Tsao MS, Nicholson AG, et al. Programmed death-ligand 1 immunohistochemistry in lung cancer: in what state is this art? J Thorac Oncol. 2015;10(7):985–9.

    Article  CAS  PubMed  Google Scholar 

  64. Krambeck AE, Dong H, Thompson RH, et al. Survivin and b7–h1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma. Clin Cancer Res. 2007;13(6):1749–56.

    Article  CAS  PubMed  Google Scholar 

  65. Lee KS, Kwak Y, Ahn S, et al. Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer. Cancer Immunol Immunother. 2017;66(7):927–39.

    Article  CAS  PubMed  Google Scholar 

  66. Ma L, Xu YL, Ding WJ, Shao HF, Teng YC. Prognostic value of Musashi-1 in endometrioid adenocarcinoma. Int J Clin Exp Pathol. 2015;8(5):4564–72.

    PubMed  PubMed Central  Google Scholar 

  67. Mei Y, Bi WL, Greenwald NF, et al. Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors. Oncotarget. 2016;7(47):76565–76.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Meniawy TM, Lake RA, McDonnell AM, Millward MJ, Nowak AK. PD-L1 on peripheral blood T lymphocytes is prognostic in patients with non-small cell lung cancer (NSCLC) treated with EGFR inhibitors. Lung Cancer. 2016;93:9–16.

    Article  PubMed  Google Scholar 

  69. Mezache L, Paniccia B, Nyinawabera A, Nuovo GJ. Enhanced expression of PD L1 in cervical intraepithelial neoplasia and cervical cancers. Mod Pathol. 2015;28(12):1594–602.

    Article  CAS  PubMed  Google Scholar 

  70. Mitteldorf C, Berisha A, Tronnier M, Pfaltz MC, Kempf W. PD-1 and PD-L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma. J Cutan Pathol. 2017;44(9):740–6.

    Article  PubMed  Google Scholar 

  71. Ness N, Andersen S, Khanehkenari MR, et al. The prognostic role of immune checkpoint markers programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) in a large, multicenter prostate cancer cohort. Oncotarget. 2017;8(16):26789–801.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Ng Kee Kwong F, Laggner U, McKinney O, Croud J, Rice A, Nicholson AG. Expression of PD-L1 correlates with pleomorphic morphology and histological patterns of non-small-cell lung carcinomas. Histopathology. 2018;72(6):1024–32.

    Article  PubMed  Google Scholar 

  73. Oguejiofor K, Galletta-Williams H, Dovedi SJ, Roberts DL, Stern PL, West CM. Distinct patterns of infiltrating CD8+ T cells in HPV+ and CD68 macrophages in HPV- oropharyngeal squamous cell carcinomas are associated with better clinical outcome but PD-L1 expression is not prognostic. Oncotarget. 2017;8(9):14416–27.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Okada S, Itoh K, Ishihara S, et al. Significance of PD-L1 expression in pulmonary metastases from head and neck squamous cell carcinoma. Surg Oncol. 2018;27(2):259–65.

    Article  PubMed  Google Scholar 

  75. Shien K, Papadimitrakopoulou VA, Wistuba II. Predictive biomarkers of response to PD-1/PD-L1 immune checkpoint inhibitors in non-small cell lung cancer. Lung Cancer. 2016;99:79–87.

    Article  PubMed  Google Scholar 

  76. Slater NA, Googe PB. PD-L1 expression in cutaneous squamous cell carcinoma correlates with risk of metastasis. J Cutan Pathol. 2016;43(8):663–70.

    Article  PubMed  Google Scholar 

  77. Sun S, Fei X, Mao Y, et al. PD-1(+) immune cell infiltration inversely correlates with survival of operable breast cancer patients. Cancer Immunol Immunother. 2014;63(4):395–406.

    Article  CAS  PubMed  Google Scholar 

  78. Tang Y, He Y, Shi L, et al. Co-expression of AFAP1-AS1 and PD-1 predicts poor prognosis in nasopharyngeal carcinoma. Oncotarget. 2017;8(24):39001–11.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Villaruz LC, Socinski MA. The clinical utility of PD-L1 testing in selecting non-small cell lung cancer patients for PD1/PD-L1-directed therapy. Clin Pharmacol Ther. 2016;100(3):212–4.

    Article  CAS  PubMed  Google Scholar 

  80. Webb JR, Milne K, Nelson BH. PD-1 and CD103 are widely coexpressed on prognostically favorable intraepithelial CD8 T Cells in human ovarian cancer. Cancer Immunol Res. 2015;3(8):926–35.

    Article  CAS  PubMed  Google Scholar 

  81. Wu CT, Chen WC, Chang YH, Lin WY, Chen MF. The role of PD-L1 in the radiation response and clinical outcome for bladder cancer. Sci Rep. 2016;6:19740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhang F, Liu Z, Cui Y, Wang G, Cao P. The clinical significance of the expression of costimulatory molecule PD-L1 in nasopharyngeal carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2008;22(9):408–10.

    PubMed  Google Scholar 

  83. Zheng H, Liu X, Zhang J, et al. Expression of PD-1 on CD4+ T cells in peripheral blood associates with poor clinical outcome in non-small cell lung cancer. Oncotarget. 2016;7(35):56233–40.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Zhou J, Gong Z, Jia Q, Wu Y, Yang ZZ, Zhu B. Programmed death ligand 1 expression and CD8+ tumor-infiltrating lymphocyte density differences between paired primary and brain metastatic lesions in non-small cell lung cancer. Biochem Biophys Res Commun. 2018;498(4):751–7.

    Article  CAS  PubMed  Google Scholar 

  85. Abbas M, Steffens S, Bellut M, et al. Intratumoral expression of programmed death ligand 1 (PD-L1) in patients with clear cell renal cell carcinoma (ccRCC). Med Oncol. 2016;33(7):80.

    Article  CAS  PubMed  Google Scholar 

  86. Aghajani MJ, Yang T, McCafferty CE, Graham S, Wu X, Niles N. Predictive relevance of programmed cell death protein 1 and tumor-infiltrating lymphocyte expression in papillary thyroid cancer. Surgery. 2018;163(1):130–6.

    Article  PubMed  Google Scholar 

  87. Ali HR, Glont SE, Blows FM, et al. PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol. 2015;26(7):1488–93.

    Article  CAS  PubMed  Google Scholar 

  88. Amatatsu M, Arigami T, Uenosono Y, et al. Programmed death-ligand 1 is a promising blood marker for predicting tumor progression and prognosis in patients with gastric cancer. Cancer Sci. 2018;109(3):814–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Arbour KC, Naidoo J, Steele KE, et al. Expression of PD-L1 and other immunotherapeutic targets in thymic epithelial tumors. PLoS ONE. 2017;12(8):e0182665.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Audrito V, Serra S, Stingi A, et al. PD-L1 up-regulation in melanoma increases disease aggressiveness and is mediated through miR-17-5p. Oncotarget. 2017;8(9):15894–911.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Azuma K, Ota K, Kawahara A, et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann Oncol. 2014;25(10):1935–40.

    Article  CAS  PubMed  Google Scholar 

  92. Badoual C, Hans S, Merillon N, et al. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res. 2013;73(1):128–38.

    Article  CAS  PubMed  Google Scholar 

  93. Baptista MZ, Sarian LO, Derchain SF, Pinto GA, Vassallo J. Prognostic significance of PD-L1 and PD-L2 in breast cancer. Hum Pathol. 2016;47(1):78–84.

    Article  CAS  PubMed  Google Scholar 

  94. Beckers RK, Selinger CI, Vilain R, et al. Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome. Histopathology. 2016;69(1):25–34.

    Article  PubMed  Google Scholar 

  95. Bellmunt J, Mullane SA, Werner L, et al. Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann Oncol. 2015;26(4):812–7.

    Article  CAS  PubMed  Google Scholar 

  96. Bertucci F, Finetti P, Colpaert C, et al. PDL1 expression in inflammatory breast cancer is frequent and predicts for the pathological response to chemotherapy. Oncotarget. 2015;6(15):13506–19.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Birnbaum DJ, Finetti P, Lopresti A, et al. Prognostic value of PDL1 expression in pancreatic cancer. Oncotarget. 2016;7(44):71198–210.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Breyer J, Wirtz RM, Otto W, et al. High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients. Cancer Immunol Immunother. 2018;67(3):403–12.

    Article  CAS  PubMed  Google Scholar 

  99. Budczies J, Bockmayr M, Denkert C, et al. Pan-cancer analysis of copy number changes in programmed death-ligand 1 (PD-L1, CD274): associations with gene expression, mutational load, and survival. Genes Chromosomes Cancer. 2016;55(8):626–39.

    Article  CAS  PubMed  Google Scholar 

  100. Cedres S, Ponce-Aix S, Zugazagoitia J, et al. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS ONE. 2015;10(3):e0121071.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Chang H, Jung WY, Kang Y, et al. Programmed death-ligand 1 expression in gastric adenocarcinoma is a poor prognostic factor in a high CD8+ tumor infiltrating lymphocytes group. Oncotarget. 2016;7(49):80426–34.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Chang K, Qu Y, Dai B, et al. PD-L1 expression in Xp11.2 translocation renal cell carcinoma: Indicator of tumor aggressiveness. Sci Rep. 2017;7(1):2074.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Chen K, Cheng G, Zhang F, et al. Prognostic significance of programmed death-1 and programmed death-ligand 1 expression in patients with esophageal squamous cell carcinoma. Oncotarget. 2016;7(21):30772–80.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Chen L, Deng H, Lu M, et al. B7–H1 expression associates with tumor invasion and predicts patient’s survival in human esophageal cancer. Int J Clin Exp Pathol. 2014;7(9):6015–23.

    PubMed  PubMed Central  Google Scholar 

  105. Chen MF, Chen PT, Chen WC, Lu MS, Lin PY, Lee KD. The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression. Oncotarget. 2016;7(7):7913–24.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Chen S, Wang RX, Liu Y, Yang WT, Shao ZM. PD-L1 expression of the residual tumor serves as a prognostic marker in local advanced breast cancer after neoadjuvant chemotherapy. Int J Cancer. 2017;140(6):1384–95.

    Article  CAS  PubMed  Google Scholar 

  107. Chen TC, Wu CT, Wang CP, et al. Associations among pretreatment tumor necrosis and the expression of HIF-1alpha and PD-L1 in advanced oral squamous cell carcinoma and the prognostic impact thereof. Oral Oncol. 2015;51(11):1004–10.

    Article  CAS  PubMed  Google Scholar 

  108. Chen Y, Sun J, Zhao H, et al. The coexpression and clinical significance of costimulatory molecules B7–H1, B7–H3, and B7–H4 in human pancreatic cancer. Onco Targets Ther. 2014;7:1465–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Chen YB, Mu CY, Huang JA. Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study. Tumori. 2012;98(6):751–5.

    Article  PubMed  Google Scholar 

  110. Chen Z, Mei J, Liu L, et al. PD-L1 expression is associated with advanced non-small cell lung cancer. Oncol Lett. 2016;12(2):921–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Chintakuntlawar AV, Rumilla KM, Smith CY, et al. Expression of PD-1 and PD-L1 in anaplastic thyroid cancer patients treated with multimodal therapy: results from a retrospective Ssudy. J Clin Endocrinol Metab. 2017;102(6):1943–50.

    Article  PubMed  Google Scholar 

  112. Cho J, Lee J, Bang H, et al. Programmed cell death-ligand 1 expression predicts survival in patients with gastric carcinoma with microsatellite instability. Oncotarget. 2017;8(8):13320–8.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Cho YA, Yoon HJ, Lee JI, Hong SP, Hong SD. Relationship between the expressions of PD-L1 and tumor-infiltrating lymphocytes in oral squamous cell carcinoma. Oral Oncol. 2011;47(12):1148–53.

    Article  CAS  PubMed  Google Scholar 

  114. Choueiri TK, Fay AP, Gray KP, et al. PD-L1 expression in nonclear-cell renal cell carcinoma. Ann Oncol. 2014;25(11):2178–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Chowdhury S, Veyhl J, Jessa F, et al. Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants. Oncotarget. 2016;7(22):32318–28.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Cierna Z, Mego M, Miskovska V, et al. Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors. Ann Oncol. 2016;27(2):300–5.

    Article  CAS  PubMed  Google Scholar 

  117. Combaz-Lair C, Galateau-Salle F, McLeer-Florin A, et al. Immune biomarkers PD-1/PD-L1 and TLR3 in malignant pleural mesotheliomas. Human Pathol. 2016;52:9–18.

    Article  CAS  Google Scholar 

  118. Cooper WA, Tran T, Vilain RE, et al. PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma. Lung Cancer. 2015;89(2):181–8.

    Article  PubMed  Google Scholar 

  119. D’Incecco A, Andreozzi M, Ludovini V, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015;112(1):95–102.

    Article  CAS  PubMed  Google Scholar 

  120. Dai C, Geng R, Wang C, et al. Concordance of immune checkpoints within tumor immune contexture and their prognostic significance in gastric cancer. Mol Oncol. 2016;10(10):1551–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Daud AI, Wolchok JD, Robert C, et al. Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma. J Clin Oncol. 2016;34(34):4102–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Dix Junqueira Pinto G, de Souza Viana L, Scapulatempo Neto C, Vicente Serrano S. Evaluation of PD-L1 expression in tumor tissue of patients with lung carcinoma and correlation with clinical and demographic data. J Immunol Res. 2016;2016:9839685.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Droeser RA, Hirt C, Viehl CT, et al. Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. Eur J Cancer. 2013;49(9):2233–42.

    Article  CAS  PubMed  Google Scholar 

  124. Enwere EK, Kornaga EN, Dean M, et al. Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer. Modern Pathol. 2017;30(4):577–86.

    Article  CAS  Google Scholar 

  125. Eto S, Yoshikawa K, Nishi M, et al. Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection. Gastric Cancer. 2016;19(2):466–71.

    Article  CAS  PubMed  Google Scholar 

  126. Fang W, Zhang J, Hong S, et al. EBV-driven LMP1 and IFN-gamma up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy. Oncotarget. 2014;5(23):12189–202.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Forest F, Patoir A, Dal Col P, et al. Nuclear grading, BAP1, mesothelin and PD-L1 expression in malignant pleural mesothelioma: prognostic implications. Pathology. 2018;50(6):635–41.

    Article  CAS  PubMed  Google Scholar 

  128. Frigola X, Inman BA, Lohse CM, et al. Identification of a soluble form of B7–H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma. Clin Cancer Res. 2011;17(7):1915–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Gadiot J, Hooijkaas AI, Kaiser AD, van Tinteren H, van Boven H, Blank C. Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer. 2011;117(10):2192–201.

    Article  CAS  PubMed  Google Scholar 

  130. Gao Q, Wang XY, Qiu SJ, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009;15(3):971–9.

    Article  CAS  PubMed  Google Scholar 

  131. Geng Y, Wang H, Lu C, et al. Expression of costimulatory molecules B7–H1, B7–H4 and Foxp3+ Tregs in gastric cancer and its clinical significance. Int J Clin Oncol. 2015;20(2):273–81.

    Article  CAS  PubMed  Google Scholar 

  132. Giraldo NA, Becht E, Pages F, et al. Orchestration and prognostic significance of immune checkpoints in the microenvironment of primary and metastatic renal cell cancer. Clin Cancer Res. 2015;21(13):3031–40.

    Article  CAS  PubMed  Google Scholar 

  133. Hamanishi J, Mandai M, Iwasaki M, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A. 2007;104(9):3360–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Hanna GJ, Woo SB, Li YY, Barletta JA, Hammerman PS, Lorch JH. Tumor PD-L1 expression is associated with improved survival and lower recurrence risk in young women with oral cavity squamous cell carcinoma. Int J Oral Maxillofac Surg. 2018;47(5):568–77.

    Article  CAS  PubMed  Google Scholar 

  135. Hata A, Katakami N, Nanjo S, et al. Programmed death-ligand 1 expression and T790M status in EGFR-mutant non-small cell lung cancer. Lung Cancer. 2017;111:182–9.

    Article  PubMed  Google Scholar 

  136. Hatogai K, Fujii S, Kojima T, et al. Large-scale comprehensive immunohistochemical biomarker analyses in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 2017;143(11):2351–61.

    Article  CAS  PubMed  Google Scholar 

  137. He J, Huo L, Ma J, et al. Expression of programmed death ligand 1 (PD-L1) in posttreatment primary inflammatory breast cancers and clinical implications. Am J Clin Pathol. 2018;149(3):253–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Heeren AM, Punt S, Bleeker MC, et al. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix. Modern Pathol. 2016;29(7):753–63.

    Article  CAS  Google Scholar 

  139. Heiland DH, Haaker G, Delev D, et al. Comprehensive analysis of PD-L1 expression in glioblastoma multiforme. Oncotarget. 2017;8(26):42214–25.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Hou J, Yu Z, Xiang R, et al. Correlation between infiltration of FOXP3+ regulatory T cells and expression of B7–H1 in the tumor tissues of gastric cancer. Exp Mol Pathol. 2014;96(3):284–91.

    Article  CAS  PubMed  Google Scholar 

  141. Huang Y, Zhang SD, McCrudden C, Chan KW, Lin Y, Kwok HF. The prognostic significance of PD-L1 in bladder cancer. Oncol Rep. 2015;33(6):3075–84.

    Article  CAS  PubMed  Google Scholar 

  142. Huynh TG, Morales-Oyarvide V, Campo MJ, et al. Programmed cell death ligand 1 expression in resected lung adenocarcinomas: association with immune microenvironment. J Thorac Oncol. 2016;11(11):1869–78.

    Article  PubMed  Google Scholar 

  143. Igawa S, Sato Y, Ryuge S, et al. Impact of PD-L1 Expression in patients with surgically resected non-small-cell lung cancer. Oncology. 2017;92(5):283–90.

    Article  CAS  PubMed  Google Scholar 

  144. Imanishi N, Hirai A, Yoneda K, et al. Programmed death-ligand 1 (PD-L1) expression in pleomorphic carcinoma of the lung. J Surg Oncol. 2018;117(7):1563–9.

    Article  CAS  PubMed  Google Scholar 

  145. Inamura K, Yokouchi Y, Kobayashi M, et al. Relationship of tumor PD-L1 (CD274) expression with lower mortality in lung high-grade neuroendocrine tumor. Cancer Med. 2017;6(10):2347–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Inoue Y, Yoshimura K, Mori K, et al. Clinical significance of PD-L1 and PD-L2 copy number gains in non-small-cell lung cancer. Oncotarget. 2016;7(22):32113–28.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Ishii H, Azuma K, Kawahara A, et al. Significance of programmed cell death-ligand 1 expression and its association with survival in patients with small cell lung cancer. J Thorac Oncol. 2015;10(3):426–30.

    Article  CAS  PubMed  Google Scholar 

  148. Ito S, Okano S, Morita M, et al. Expression of PD-L1 and HLA class I in esophageal squamous cell carcinoma: prognostic factors for patient outcome. Ann Surg Oncol. 2016;23(Suppl. 4):508–15.

    Article  PubMed  Google Scholar 

  149. Jesinghaus M, Steiger K, Slotta-Huspenina J, et al. Increased intraepithelial CD3+ T-lymphocytes and high PD-L1 expression on tumor cells are associated with a favorable prognosis in esophageal squamous cell carcinoma and allow prognostic immunogenic subgrouping. Oncotarget. 2017;8(29):46756–68.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Jiang D, Song Q, Wang H, et al. Independent prognostic role of PD-L1expression in patients with esophageal squamous cell carcinoma. Oncotarget. 2017;8(5):8315–29.

    Article  PubMed  Google Scholar 

  151. Jiang Y, Lo AWI, Wong A, et al. Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma. Oncotarget. 2017;8(18):30175–89.

    Article  PubMed  PubMed Central  Google Scholar 

  152. Jin S, Xu B, Yu L, et al. The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy. Oncotarget. 2017;8(24):38850–62.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Jung HI, Jeong D, Ji S, et al. Overexpression of PD-L1 and PD-L2 is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Res Treat. 2017;49(1):246–54.

    Article  CAS  PubMed  Google Scholar 

  154. Kang HJ, Lee IS, Park YS, et al. Biomarkers of EBV-positive gastric cancers: loss of PTEN expression is associated with poor prognosis and nodal metastasis. Ann Surg Oncol. 2016;23(11):3684–92.

    Article  PubMed  Google Scholar 

  155. Karim R, Jordanova ES, Piersma SJ, et al. Tumor-expressed B7–H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma. Clin Cancer Res. 2009;15(20):6341–7.

    Article  CAS  PubMed  Google Scholar 

  156. Kawazoe A, Kuwata T, Kuboki Y, et al. Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein-Barr virus status in a large cohort of gastric cancer patients. Gastric Cancer. 2017;20(3):407–15.

    Article  CAS  PubMed  Google Scholar 

  157. Kim C, Kim EK, Jung H, et al. Prognostic implications of PD-L1 expression in patients with soft tissue sarcoma. BMC Cancer. 2016;16:434.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Kim HS, Lee JY, Lim SH, et al. Association between PD-L1 and HPV status and the prognostic value of PD-L1 in oropharyngeal squamous cell carcinoma. Cancer Res Treat. 2016;48(2):527–36.

    Article  CAS  PubMed  Google Scholar 

  159. Kim J, Kim S, Lee HS, et al. Prognostic implication of programmed cell death 1 protein and its ligand expressions in endometrial cancer. Gynecol Oncol. 2018;149(2):381–7.

    Article  CAS  PubMed  Google Scholar 

  160. Kim JW, Nam KH, Ahn SH, et al. Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer. Gastric Cancer. 2016;19(1):42–52.

    Article  CAS  PubMed  Google Scholar 

  161. Kim MY, Koh J, Kim S, Go H, Jeon YK, Chung DH. Clinicopathological analysis of PD-L1 and PD-L2 expression in pulmonary squamous cell carcinoma: Comparison with tumor-infiltrating T cells and the status of oncogenic drivers. Lung Cancer. 2015;88(1):24–33.

    Article  PubMed  Google Scholar 

  162. Kim R, Keam B, Kwon D, et al. Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma. World J Gastroenterol. 2016;22(37):8389–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Kim SH, Park WS, Park EY, et al. The prognostic value of BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 tissue markers in localized renal cell carcinoma: a retrospective study of tissue microarrays using immunohistochemistry. PLoS ONE. 2017;12(6):e0179610.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  164. Kluger HM, Zito CR, Turcu G, et al. PD-L1 studies across tumor types, its differential expression and predictive value in patients treated with immune checkpoint inhibitors. Clin Cancer Res. 2017;23(15):4270–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Koh J, Ock CY, Kim JW, et al. Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer patients. Oncotarget. 2017;8(16):26356–67.

    Article  PubMed  PubMed Central  Google Scholar 

  166. Koirala P, Roth ME, Gill J, et al. Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma. Sci Rep. 2016;6:30093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Lee LH, Cavalcanti MS, Segal NH, et al. Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Mod Pathol. 2016;29(11):1433–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Lee VH, Lo AW, Leung CY, et al. Correlation of PD-L1 expression of tumor cells with survival outcomes after radical intensity-modulated radiation therapy for non-metastatic nasopharyngeal carcinoma. PLoS ONE. 2016;11(6):e0157969.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  169. Leng C, Li Y, Qin J, et al. Relationship between expression of PD-L1 and PD-L2 on esophageal squamous cell carcinoma and the antitumor effects of CD8(+) T cells. Oncol Rep. 2016;35(2):699–708.

    Article  CAS  PubMed  Google Scholar 

  170. Li M, Li H, Liu F, et al. Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers: implications for personalized cancer therapy. J Ovarian Res. 2017;10(1):9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  171. Li Z, Dong P, Ren M, et al. PD-L1 expression is associated with tumor FOXP3(+) regulatory T-cell infiltration of breast cancer and poor prognosis of patient. J Cancer. 2016;7(7):784–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Li Z, Lai Y, Sun L, et al. PD-L1 expression is associated with massive lymphocyte infiltration and histology in gastric cancer. Hum Pathol. 2016;55:182–9.

    Article  PubMed  CAS  Google Scholar 

  173. Lim SH, Hong M, Ahn S, et al. Changes in tumour expression of programmed death-ligand 1 after neoadjuvant concurrent chemoradiotherapy in patients with squamous oesophageal cancer. Eur J Cancer. 2016;52:1–9.

    Article  CAS  PubMed  Google Scholar 

  174. Lin C, Chen X, Li M, et al. Programmed death-ligand 1 expression predicts tyrosine kinase inhibitor response and better prognosis in a cohort of patients with epidermal growth factor receptor mutation-positive lung adenocarcinoma. Clin Lung Cancer. 2015;16(5):e25-35.

    Article  CAS  PubMed  Google Scholar 

  175. Lin YM, Sung WW, Hsieh MJ, et al. High PD-L1 expression correlates with metastasis and poor prognosis in oral squamous cell carcinoma. PLoS ONE. 2015;10(11):e0142656.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  176. Liu R, Peng K, Yu Y, et al. Prognostic value of immunoscore and PD-L1 expression in metastatic colorectal cancer patients with different RAS status after palliative operation. BioMed Res Int. 2018;2018:5920608.

    PubMed  PubMed Central  Google Scholar 

  177. Liu Y, Carlsson R, Ambjorn M, et al. PD-L1 expression by neurons nearby tumors indicates better prognosis in glioblastoma patients. J Neurosci. 2013;33(35):14231–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Loos M, Giese NA, Kleeff J, et al. Clinical significance and regulation of the costimulatory molecule B7–H1 in pancreatic cancer. Cancer Lett. 2008;268(1):98–109.

    Article  CAS  PubMed  Google Scholar 

  179. Loos M, Langer R, Schuster T, et al. Clinical significance of the costimulatory molecule B7–H1 in Barrett carcinoma. Ann Thorac Surg. 2011;91(4):1025–31.

    Article  PubMed  Google Scholar 

  180. Madore J, Strbenac D, Vilain R, et al. PD-L1 negative status is associated with lower mutation burden, differential expression of immune-related genes, and worse survival in stage III melanoma. Clin Cancer Res. 2016;22(15):3915–23.

    Article  CAS  PubMed  Google Scholar 

  181. Mansfield AS, Roden AC, Peikert T, et al. B7–H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thorac Oncol. 2014;9(7):1036–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Mao Y, Li W, Chen K, et al. B7–H1 and B7–H3 are independent predictors of poor prognosis in patients with non-small cell lung cancer. Oncotarget. 2015;6(5):3452–61.

    Article  PubMed  Google Scholar 

  183. Maruse Y, Kawano S, Jinno T, et al. Significant association of increased PD-L1 and PD-1 expression with nodal metastasis and a poor prognosis in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2018;47(7):836–45.

    Article  CAS  PubMed  Google Scholar 

  184. Massi D, Brusa D, Merelli B, et al. PD-L1 marks a subset of melanomas with a shorter overall survival and distinct genetic and morphological characteristics. Ann Oncol. 2014;25(12):2433–42.

    Article  CAS  PubMed  Google Scholar 

  185. Massi D, Brusa D, Merelli B, et al. The status of PD-L1 and tumor-infiltrating immune cells predict resistance and poor prognosis in BRAFi-treated melanoma patients harboring mutant BRAFV600. Ann Oncol. 2015;26(9):1980–7.

    Article  CAS  PubMed  Google Scholar 

  186. Mills AM, Peres LC, Meiss A, et al. Targetable immune regulatory molecule expression in high-grade serous ovarian carcinomas in African American women: a study of PD-L1 and IDO in 112 cases from the African American Cancer Epidemiology Study (AACES). Int J Gynecol Pathol. 2019;38(2):157–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Miyazaki T, Ishikawa E, Matsuda M, et al. Assessment of PD-1 positive cells on initial and secondary resected tumor specimens of newly diagnosed glioblastoma and its implications on patient outcome. J Neurooncol. 2017;133(2):277–85.

    Article  CAS  PubMed  Google Scholar 

  188. Momose K, Yamasaki M, Tanaka K, et al. MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer. Oncol Lett. 2017;14(1):958–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Mori H, Kubo M, Yamaguchi R, et al. The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer. Oncotarget. 2017;8(9):15584–92.

    Article  PubMed  PubMed Central  Google Scholar 

  190. Mu CY, Huang JA, Chen Y, Chen C, Zhang XG. High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol. 2011;28(3):682–8.

    Article  CAS  PubMed  Google Scholar 

  191. Muenst S, Schaerli AR, Gao F, et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2014;146(1):15–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Mukaigawa T, Hayashi R, Hashimoto K, Ugumori T, Hato N, Fujii S. Programmed death ligand-1 expression is associated with poor disease free survival in salivary gland carcinomas. J Surg Oncol. 2016;114(1):36–43.

    Article  CAS  PubMed  Google Scholar 

  193. Nduom EK, Wei J, Yaghi NK, et al. PD-L1 expression and prognostic impact in glioblastoma. Neurooncol. 2016;18(2):195–205.

    CAS  Google Scholar 

  194. Nguyen BH, Montgomery R, Fadia M, Wang J, Ali S. PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma. Asia Pac J Clin Oncol. 2018;14(1):69–73.

    Article  PubMed  Google Scholar 

  195. Nomi T, Sho M, Akahori T, et al. Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res. 2007;13(7):2151–7.

    Article  CAS  PubMed  Google Scholar 

  196. Ock CY, Kim S, Keam B, et al. PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Oncotarget. 2016;7(13):15901–14.

    Article  PubMed  PubMed Central  Google Scholar 

  197. Ohigashi Y, Sho M, Yamada Y, et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res. 2005;11(8):2947–53.

    Article  CAS  PubMed  Google Scholar 

  198. Ohue Y, Kurose K, Nozawa R, et al. Survival of lung adenocarcinoma patients predicted from expression of PD-L1, Galectin-9, and XAGE1 (GAGED2a) on tumor cells and tumor-infiltrating T cells. Cancer Immunol Res. 2016;4(12):1049–60.

    Article  CAS  PubMed  Google Scholar 

  199. Oliveira-Costa JP, de Carvalho AF, da Silveira da GG, et al. Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells. Oncotarget. 2015;6(25):20902–20.

    Article  PubMed  PubMed Central  Google Scholar 

  200. Padda SK, Riess JW, Schwartz EJ, et al. Diffuse high intensity PD-L1 staining in thymic epithelial tumors. J Thorac Oncol. 2015;10(3):500–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Park IH, Kong SY, Ro JY, et al. Prognostic implications of tumor-infiltrating lymphocytes in association with programmed death ligand 1 expression in early-stage breast cancer. Clin Breast Cancer. 2016;16(1):51–8.

    Article  CAS  PubMed  Google Scholar 

  202. Qin T, Zeng YD, Qin G, et al. High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer. Oncotarget. 2015;6(32):33972–81.

    Article  PubMed  PubMed Central  Google Scholar 

  203. Qing Y, Li Q, Ren T, et al. Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer. Drug Des Dev Ther. 2015;9:901–9.

    Article  CAS  Google Scholar 

  204. Ren M, Dai B, Kong YY, Lv JJ, Cai X. PD-L1 expression in tumour-infiltrating lymphocytes is a poor prognostic factor for primary acral melanoma patients. Histopathology. 2018;73(3):386–96.

    Article  PubMed  Google Scholar 

  205. Roper E, Lum T, Palme CE, et al. PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma. Pathology. 2017;49(5):499–505.

    Article  CAS  PubMed  Google Scholar 

  206. Sabatier R, Finetti P, Mamessier E, et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget. 2015;6(7):5449–64.

    Article  PubMed  Google Scholar 

  207. Saito R, Abe H, Kunita A, Yamashita H, Seto Y, Fukayama M. Overexpression and gene amplification of PD-L1 in cancer cells and PD-L1(+) immune cells in Epstein-Barr virus-associated gastric cancer: the prognostic implications. Mod Pathol. 2017;30(3):427–39.

    Article  CAS  PubMed  Google Scholar 

  208. Satgunaseelan L, Gupta R, Madore J, et al. Programmed cell death-ligand 1 expression in oral squamous cell carcinoma is associated with an inflammatory phenotype. Pathology. 2016;48(6):574–80.

    Article  CAS  PubMed  Google Scholar 

  209. Schaper-Gerhardt K, Okoye S, Herbst R, et al. PD-L1 status does not predict the outcome of BRAF inhibitor therapy in metastatic melanoma. Eur J Cancer. 2018;88:67–76.

    Article  CAS  PubMed  Google Scholar 

  210. Schmidt LH, Kummel A, Gorlich D, et al. PD-1 and PD-L1 expression in NSCLC indicate a favorable prognosis in defined subgroups. PLoS ONE. 2015;10(8):e0136023.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  211. Semaan A, Dietrich D, Bergheim D, et al. CXCL12 expression and PD-L1 expression serve as prognostic biomarkers in HCC and are induced by hypoxia. Virchows Arch. 2017;470(2):185–96.

    Article  CAS  PubMed  Google Scholar 

  212. Sepesi B, Cuentas EP, Canales JR, et al. Programmed death cell ligand 1 (PD-L1) is associated with survival in stage I non-small cell lung cancer. Semin Thorac Cardiovasc Surg. 2017;29(3):408–15.

    Article  PubMed  Google Scholar 

  213. Shi RL, Qu N, Luo TX, et al. Programmed death-ligand 1 expression in papillary thyroid cancer and its correlation with clinicopathologic factors and recurrence. Thyroid. 2017;27(4):537–45.

    Article  CAS  PubMed  Google Scholar 

  214. Shi SJ, Wang LJ, Wang GD, et al. B7–H1 expression is associated with poor prognosis in colorectal carcinoma and regulates the proliferation and invasion of HCT116 colorectal cancer cells. PLoS ONE. 2013;8(10):e76012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Shimoji M, Shimizu S, Sato K, et al. Clinical and pathologic features of lung cancer expressing programmed cell death ligand 1 (PD-L1). Lung Cancer. 2016;98:69–75.

    Article  PubMed  Google Scholar 

  216. Shin SJ, Jeon YK, Kim PJ, et al. Clinicopathologic analysis of PD-L1 and PD-L2 expression in renal cell carcinoma: association with oncogenic proteins status. Ann Surg Oncol. 2016;23(2):694–702.

    Article  PubMed  Google Scholar 

  217. Sterlacci W, Fiegl M, Droeser RA, Tzankov A. Expression of PD-L1 identifies a subgroup of more aggressive non-small cell carcinomas of the lung. Pathobiology. 2016;83(5):267–75.

    Article  CAS  PubMed  Google Scholar 

  218. Straub M, Drecoll E, Pfarr N, et al. CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity. Oncotarget. 2016;7(11):12024–34.

    Article  PubMed  PubMed Central  Google Scholar 

  219. Sun JM, Zhou W, Choi YL, et al. Prognostic significance of PD-L1 in patients with non-small cell lung cancer: a large cohort study of surgically resected cases. J Thorac Oncol. 2016;11(7):1003–11.

    Article  CAS  PubMed  Google Scholar 

  220. Takada K, Okamoto T, Shoji F, et al. Clinical significance of PD-L1 protein expression in surgically resected primary lung adenocarcinoma. J Thorac Oncol. 2016;11(11):1879–90.

    Article  PubMed  Google Scholar 

  221. Takada K, Okamoto T, Toyokawa G, et al. The expression of PD-L1 protein as a prognostic factor in lung squamous cell carcinoma. Lung Cancer. 2017;104:7–15.

    Article  PubMed  Google Scholar 

  222. Tamura T, Ohira M, Tanaka H, et al. Programmed death-1 ligand-1 (PDL1) expression is associated with the prognosis of patients with stage II/III gastric cancer. Anticancer Res. 2015;35(10):5369–76.

    CAS  PubMed  Google Scholar 

  223. Tanaka K, Miyata H, Sugimura K, et al. Negative influence of programmed death-1-ligands on the survival of esophageal cancer patients treated with chemotherapy. Cancer Sci. 2016;107(6):726–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Tang Y, Fang W, Zhang Y, et al. The association between PD-L1 and EGFR status and the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs. Oncotarget. 2015;6(16):14209–19.

    Article  PubMed  PubMed Central  Google Scholar 

  225. Teglasi V, Reiniger L, Fabian K, et al. Evaluating the significance of density, localization, and PD-1/PD-L1 immunopositivity of mononuclear cells in the clinical course of lung adenocarcinoma patients with brain metastasis. Neurooncol. 2017;19(8):1058–67.

    CAS  Google Scholar 

  226. Tessier-Cloutier B, Kalloger SE, Al-Kandari M, et al. Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma. BMC Cancer. 2017;17(1):618.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  227. Thierauf J, Veit JA, Affolter A, et al. Identification and clinical relevance of PD-L1 expression in primary mucosal malignant melanoma of the head and neck. Melanoma Res. 2015;25(6):503–9.

    Article  CAS  PubMed  Google Scholar 

  228. Thompson RH, Gillett MD, Cheville JC, et al. Costimulatory B7–H1 in renal cell carcinoma patients: indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A. 2004;101(49):17174–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Thompson RH, Kuntz SM, Leibovich BC, et al. Tumor B7–H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 2006;66(7):3381–5.

    Article  CAS  PubMed  Google Scholar 

  230. Tokito T, Azuma K, Kawahara A, et al. Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy. Eur J Cancer. 2016;55:7–14.

    Article  CAS  PubMed  Google Scholar 

  231. Toyokawa G, Takada K, Okamoto T, et al. Relevance between programmed death ligand 1 and radiologic invasiveness in pathologic stage I lung adenocarcinoma. Ann Thorac Surg. 2017;103(6):1750–7.

    Article  PubMed  Google Scholar 

  232. Tsang JY, Au WL, Lo KY, et al. PD-L1 expression and tumor infiltrating PD-1+ lymphocytes associated with outcome in HER2+ breast cancer patients. Breast Cancer Res Treat. 2017;162(1):19–30.

    Article  CAS  PubMed  Google Scholar 

  233. Tsao MS, Le Teuff G, Shepherd FA, et al. PD-L1 protein expression assessed by immunohistochemistry is neither prognostic nor predictive of benefit from adjuvant chemotherapy in resected non-small cell lung cancer. Ann Oncol. 2017;28(4):882–9.

    Article  PubMed  PubMed Central  Google Scholar 

  234. Tsuruoka K, Horinouchi H, Goto Y, et al. PD-L1 expression in neuroendocrine tumors of the lung. Lung Cancer. 2017;108:115–20.

    Article  PubMed  Google Scholar 

  235. Tsutsumi S, Saeki H, Nakashima Y, et al. Programmed death-ligand 1 expression at tumor invasive front is associated with epithelial-mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma. Cancer Sci. 2017;108(6):1119–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Ukpo OC, Thorstad WL, Lewis JS Jr. B7–H1 expression model for immune evasion in human papillomavirus-related oropharyngeal squamous cell carcinoma. Head Neck Pathol. 2013;7(2):113–21.

    Article  PubMed  Google Scholar 

  237. Umemoto Y, Okano S, Matsumoto Y, et al. Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy. J Gastroenterol. 2015;50(1):65–75.

    Article  CAS  PubMed  Google Scholar 

  238. Uruga H, Bozkurtlar E, Huynh TG, et al. Programmed cell death ligand (PD-L1) expression in stage II and III lung adenocarcinomas and nodal metastases. J Thorac Oncol. 2017;12(3):458–66.

    Article  PubMed  Google Scholar 

  239. Vallonthaiel AG, Malik PS, Singh V, et al. Clinicopathologic correlation of programmed death ligand-1 expression in non-small cell lung carcinomas: a report from India. Ann Diagn Pathol. 2017;31:56–61.

    Article  PubMed  Google Scholar 

  240. Vassilakopoulou M, Avgeris M, Velcheti V, et al. Evaluation of PD-L1 expression and associated tumor-infiltrating lymphocytes in laryngeal squamous cell carcinoma. Clin Cancer Res. 2016;22(3):704–13.

    Article  CAS  PubMed  Google Scholar 

  241. Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest. 2014;94(1):107–16.

    Article  CAS  PubMed  Google Scholar 

  242. Wakita A, Motoyama S, Nanjo H, et al. PD-L1 expression is a prognostic factor in patients with thoracic esophageal cancer treated without adjuvant chemotherapy. Anticancer Res. 2017;37(3):1433–41.

    Article  CAS  PubMed  Google Scholar 

  243. Walter D, Herrmann E, Schnitzbauer AA, et al. PD-L1 expression in extrahepatic cholangiocarcinoma. Histopathology. 2017;71(3):383–92.

    Article  PubMed  Google Scholar 

  244. Wang L, Ma Q, Chen X, Guo K, Li J, Zhang M. Clinical significance of B7–H1 and B7–1 expressions in pancreatic carcinoma. World J Surg. 2010;34(5):1059–65.

    Article  PubMed  Google Scholar 

  245. Wang L, Ma Q, Li D, et al. Indoleamine 2, 3-dioxygenase and B7–H1 expressions as prognostic and follow-up markers in human pancreatic carcinoma. Pathol Res Pract. 2018;214(9):1309–14.

    Article  CAS  PubMed  Google Scholar 

  246. Wang L, Ren F, Wang Q, et al. Significance of programmed death ligand 1 (PD-L1) immunohistochemical expression in colorectal cancer. Mol Diagn Ther. 2016;20(2):175–81.

    Article  CAS  PubMed  Google Scholar 

  247. Wang Q, Liu F, Liu L. Prognostic significance of PD-L1 in solid tumor: an updated meta-analysis. Medicine. 2017;96(18):e6369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Wang Q, Lou W, Di W, Wu X. Prognostic value of tumor PD-L1 expression combined with CD8+ tumor infiltrating lymphocytes in high grade serous ovarian cancer. Int Immunopharmacol. 2017;52:7–14.

    Article  CAS  PubMed  Google Scholar 

  249. Webb JR, Milne K, Kroeger DR, Nelson BH. PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer. Gynecol Oncol. 2016;141(2):293–302.

    Article  CAS  PubMed  Google Scholar 

  250. Weissferdt A, Fujimoto J, Kalhor N, et al. Expression of PD-1 and PD-L1 in thymic epithelial neoplasms. Modern Pathol. 2017;30(6):826–33.

    Article  CAS  Google Scholar 

  251. Wu C, Zhu Y, Jiang J, Zhao J, Zhang XG, Xu N. Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem. 2006;108(1):19–24.

    Article  PubMed  Google Scholar 

  252. Wu S, Shi X, Sun J, et al. The significance of programmed cell death ligand 1 expression in resected lung adenocarcinoma. Oncotarget. 2017;8(10):16421–9.

    Article  PubMed  PubMed Central  Google Scholar 

  253. Xu M, Zhang B, Zhang M, et al. Clinical relevance of expression of B7–H1 and B7–H4 in ovarian cancer. Oncol Lett. 2016;11(4):2815–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Xylinas E, Robinson BD, Kluth LA, et al. Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder. Eur J Surg Oncol. 2014;40(1):121–7.

    Article  CAS  PubMed  Google Scholar 

  255. Yagi T, Baba Y, Ishimoto T, et al. PD-L1 expression, tumor-infiltrating lymphocytes, and clinical outcome in patients with surgically resected esophageal cancer. Ann Surg. 2019;269(3):471–8.

    Article  PubMed  Google Scholar 

  256. Yamaki S, Yanagimoto H, Tsuta K, Ryota H, Kon M. PD-L1 expression in pancreatic ductal adenocarcinoma is a poor prognostic factor in patients with high CD8+ tumor-infiltrating lymphocytes: highly sensitive detection using phosphor-integrated dot staining. Int J Clin Oncol. 2017;22(4):726–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Yokoyama S, Miyoshi H, Nishi T, et al. Clinicopathologic and prognostic implications of programmed death ligand 1 expression in thymoma. Ann Thorac Surg. 2016;101(4):1361–9.

    Article  PubMed  Google Scholar 

  258. Yuan J, Zhang J, Zhu Y, et al. Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance. Oncotarget. 2016;7(26):39671–9.

    Article  PubMed  PubMed Central  Google Scholar 

  259. Yvorel V, Patoir A, Casteillo F, et al. PD-L1 expression in pleomorphic, spindle cell and giant cell carcinoma of the lung is related to TTF-1, p40 expression and might indicate a worse prognosis. PLoS ONE. 2017;12(7):e0180346.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  260. Zeng J, Zhang XK, Chen HD, Zhong ZH, Wu QL, Lin SX. Expression of programmed cell death-ligand 1 and its correlation with clinical outcomes in gliomas. Oncotarget. 2016;7(8):8944–55.

    Article  PubMed  PubMed Central  Google Scholar 

  261. Zhang J, Fang W, Qin T, et al. Co-expression of PD-1 and PD-L1 predicts poor outcome in nasopharyngeal carcinoma. Med Oncol. 2015;32(3):86.

    Article  PubMed  CAS  Google Scholar 

  262. Zhang L, Qiu M, Jin Y, et al. Programmed cell death ligand 1 (PD-L1) expression on gastric cancer and its relationship with clinicopathologic factors. Int J Clin Exp Pathol. 2015;8(9):11084–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  263. Zhang W, Pang Q, Zhang X, et al. Programmed death-ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor. Cancer Sci. 2017;108(4):590–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  264. Zhou Y, Shi D, Miao J, et al. PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load. Sci Rep. 2017;7:43627.

    Article  PubMed  PubMed Central  Google Scholar 

  265. Zhu H, Qin H, Huang Z, et al. Clinical significance of programmed death ligand-1 (PD-L1) in colorectal serrated adenocarcinoma. Int J Clin Exp Pathol. 2015;8(8):9351–9.

    PubMed  PubMed Central  Google Scholar 

  266. Zhu J, Wen H, Ju X, Bi R, Zuo W, Wu X. Clinical significance of programmed death ligand-1 and intra-tumoral CD8+ T lymphocytes in ovarian carcinosarcoma. PLoS ONE. 2017;12(1):e0170879.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  267. Zhu X, Lang J. The significance and therapeutic potential of PD-1 and its ligands in ovarian cancer: a systematic review. Gynecol Oncol. 2016;142(1):184–9.

    Article  CAS  PubMed  Google Scholar 

  268. Crispin H, Agarwal AM, Salama ME, et al. Correlation of tumor programmed death ligand-1 (PD-L1) expression and response to treatment with high-dose interleukin-2 (HD IL-2) in clear cell metastatic renal cell carcinoma (ccmRCC). J Clin Oncol. 2014;32(15_Suppl):e15584.

    Article  Google Scholar 

  269. Nguyen LT, Ohashi PS. Clinical blockade of PD1 and LAG3–potential mechanisms of action. Nat Rev Immunol. 2015;15(1):45–56.

    Article  CAS  PubMed  Google Scholar 

  270. Kruger S, Ilmer M, Kobold S, et al. Advances in cancer immunotherapy 2019: latest trends. J Exp Clin Cancer Res. 2019;38(1):268.

    Article  PubMed  PubMed Central  Google Scholar 

  271. Ancevski Hunter K, Socinski MA, Villaruz LC. PD-L1 testing in guiding patient selection for PD-1/PD-L1 inhibitor therapy in lung cancer. Mol Diagn Ther. 2018;22(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  272. Masucci GV, Cesano A, Hawtin R, et al. Validation of biomarkers to predict response to immunotherapy in cancer: Volume I: pre-analytical and analytical validation. J Immunother Cancer. 2016;4:76.

    Article  PubMed  PubMed Central  Google Scholar 

  273. Dobbin KK, Cesano A, Alvarez J, et al. Validation of biomarkers to predict response to immunotherapy in cancer: Volume II: clinical validation and regulatory considerations. J Immunother Cancer. 2016;4:77.

    Article  PubMed  PubMed Central  Google Scholar 

  274. Aguiar PN Jr, De Mello RA, Hall P, Tadokoro H, Lima LG. PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data. Immunotherapy. 2017;9(6):499–506.

    Article  CAS  PubMed  Google Scholar 

  275. Muller T, Braun M, Dietrich D, et al. PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma. Oncotarget. 2017;8(32):52889–900.

    Article  PubMed  PubMed Central  Google Scholar 

  276. Lee Y, Shin JH, Longmire M, et al. CD44+ cells in head and neck squamous cell carcinoma suppress T-cell-mediated immunity by selective constitutive and inducible expression of PD-L1. Clin Cancer Res. 2016;22(14):3571–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  277. Wankowicz SAM, Werner L, Orsola A, et al. Differential expression of PD-L1 in high grade T1 vs muscle invasive bladder carcinoma and its prognostic implications. J Urol. 2017;198(4):817–23.

    Article  CAS  PubMed  Google Scholar 

  278. Inman BA, Sebo TJ, Frigola X, et al. PD-L1 (B7–H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer. 2007;109(8):1499–505.

    Article  CAS  PubMed  Google Scholar 

  279. Andre T, Shiu KK, Kim TW, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;383(23):2207–18.

    Article  CAS  PubMed  Google Scholar 

  280. Hino R, Kabashima K, Kato Y, et al. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer. 2010;116(7):1757–66.

    Article  PubMed  Google Scholar 

  281. Hou Y, Nitta H, Wei L, et al. PD-L1 expression and CD8-positive T cells are associated with favorable survival in HER2-positive invasive breast cancer. Breast J. 2018;24(6):911–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  282. Thompson ED, Taube JM, Asch-Kendrick RJ, et al. PD-L1 expression and the immune microenvironment in primary invasive lobular carcinomas of the breast. Mod Pathol. 2017;30(11):1551–60.

    Article  CAS  PubMed  Google Scholar 

  283. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.

    Article  CAS  PubMed  Google Scholar 

  284. Boussiotis VA. Molecular and biochemical aspects of the PD-1 checkpoint pathway. N Engl J Med. 2016;375(18):1767–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  285. Suzuki A, Itami S, Ohishi M, et al. Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation. Cancer Res. 2003;63(3):674–81.

    CAS  PubMed  Google Scholar 

  286. Chen J, Jiang CC, Jin L, Zhang XD. Regulation of PD-L1: a novel role of pro-survival signalling in cancer. Ann Oncol. 2016;27(3):409–16.

    Article  CAS  PubMed  Google Scholar 

  287. Jiang X, Wang J, Deng X, et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Mol Cancer. 2019;18(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  288. Ilie M, Hofman V, Dietel M, Soria JC, Hofman P. Assessment of the PD-L1 status by immunohistochemistry: challenges and perspectives for therapeutic strategies in lung cancer patients. Virchows Arch. 2016;468(5):511–25.

    Article  CAS  PubMed  Google Scholar 

  289. Lawson NL, Dix CI, Scorer PW, et al. Mapping the binding sites of antibodies utilized in programmed cell death ligand-1 predictive immunohistochemical assays for use with immuno-oncology therapies. Mod Pathol. 2020;33(4):518–30.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Ramy R. Saleh and Jordan L. Scott have equal contribution as first author.

Authors and Affiliations

  1. Department of Medical Oncology, McGill University, Montreal, QC, Canada

    Ramy R. Saleh

  2. Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, Toronto, ON, Canada

    Jordan L. Scott, Nicholas Meti, Danielle Perlon & Eitan Amir

  3. Information Specialist, Library and Information Services, Princess Margaret Cancer Centre, Toronto, ON, Canada

    Rouhi Fazelzad

  4. Hospital Clinico San Carlos and Instituto de Investigación Sanitaria San Carlos (IdISSC), and Centro Regional de Investigaciones Biomedicas (CRIB), Centro de Investigación Biomédica en Red Cáncerci (CIBERONC), Universidad Castilla La Mancha (UCLM), Madrid, Spain

    Alberto Ocana

Authors
  1. Ramy R. Saleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jordan L. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicholas Meti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Danielle Perlon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rouhi Fazelzad
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alberto Ocana
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eitan Amir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eitan Amir.

Ethics declarations

Funding

No sources of funding were used for the preparation of this article.

Conflicts of interest/Competing interests

Eitan Amir reports personal fees from Genentech/Roche, Apobiologix, Myriad Genetics, and Agendia, outside the submitted work. Ramy Saleh reports personal fees from Roche outside the submitted work. Jordan Scott reports no conflicts of interest. Danielle Perlon reports no conflicts of interest. Alberto Ocana reports personal fees from Daychi-Sankyo, Servier, Entrechem, and CancerAppy and travel support from Merck, outside the submitted work. Nicholas Meti reports no conflicts of interest. Rouhi Fazelzad reports no conflicts of interest.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

The data underlying this article will be shared on reasonable request to the corresponding author.

Code availability

Not applicable.

Authors’ contributions

Concept and design: all authors. Financial support: not applicable. Collection and assembly of data: RS and JLS. Data analysis and interpretation: all authors. Manuscript writing: all authors. Final approval of manuscript: all authors. RS and JS contributed equally as first author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saleh, R.R., Scott, J.L., Meti, N. et al. Prognostic Value of Programmed Death Ligand-1 Expression in Solid Tumors Irrespective of Immunotherapy Exposure: A Systematic Review and Meta-Analysis. Mol Diagn Ther 26, 153–168 (2022). https://doi.org/10.1007/s40291-022-00576-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40291-022-00576-4

Search

Navigation