Skip to main content

Advertisement

SpringerLink
Log in

Regulation of PD-1/PD-L1 Pathway in Cancer by Noncoding RNAs

  • Review
  • Published:
Pathology & Oncology Research

Abstract

Immune checkpoint blockade has demonstrated significant anti-tumor immunity in an array of cancer types, yet the underlying regulatory mechanism of it is still obscure, and many problems remain to be solved. As an inhibitory costimulatory signal of T-cells, the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway can paralyze T-cells at the tumor site, enabling the immune escape of tumor cells. Although many antibodies targeting PD-1/PD-L1 have been developed to block their interaction for the treatment of cancer, the reduced response rate and resistance to the therapies call for further comprehension of this pathway in the tumor microenvironment. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two main types of noncoding RNAs that play critical parts in the regulation of immune response in tumorigenesis, including the PD-1/PD-L1 pathway. Here we summarize the most recent studies on the control of this pathway by noncoding RNAs in cancer and hopefully will offer new insights into immune checkpoint blockade therapies.

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

Data Availability

The datasets analyzed in this article are available from the corresponding author on reasonable request.

References

  1. Teng MW et al (2008) Immune-mediated dormancy: an equilibrium with cancer. J Leukoc Biol 84(4):988–993

    Article  CAS  PubMed  Google Scholar 

  2. Schneider H et al (2006) Reversal of the TCR stop signal by CTLA-4. Science 313(5795):1972–1975

    Article  CAS  PubMed  Google Scholar 

  3. Ishida Y et al (1992) Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 11(11):3887–3895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dong H et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800

    Article  CAS  PubMed  Google Scholar 

  5. Dong H et al (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 5(12):1365–1369

    Article  CAS  PubMed  Google Scholar 

  6. Freeman GJ et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7):1027–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhang X et al (2004) Structural and functional analysis of the costimulatory receptor programmed death-1. Immunity 20(3):337–347

    Article  CAS  PubMed  Google Scholar 

  8. Lesterhuis WJ, Steer H, Lake RA (2011) PD-L2 is predominantly expressed by Th2 cells. Mol Immunol 49(1–2):1–3

    Article  CAS  PubMed  Google Scholar 

  9. Chen L (2004) Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 4(5):336–347

    Article  CAS  PubMed  Google Scholar 

  10. Sheppard KA et al (2004) PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta. FEBS Lett 574(1–3):37–41

    Article  CAS  PubMed  Google Scholar 

  11. Francisco LM, Sage PT, Sharpe AH (2010) The PD-1 pathway in tolerance and autoimmunity. Immunol Rev 236:219–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zamani MR et al (2016) PD-1/PD-L and autoimmunity: a growing relationship. Cell Immunol 310:27–41

    Article  CAS  PubMed  Google Scholar 

  13. Sharpe AH et al (2007) The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol 8(3):239–245

    Article  CAS  PubMed  Google Scholar 

  14. Butte MJ et al (2007) Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 27(1):111–122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Schadendorf D et al (2015) Pooled analysis of Long-term survival data from phase II and phase III trials of Ipilimumab in Unresectable or metastatic melanoma. J Clin Oncol 33(17):1889–1894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wolchok JD et al (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369(2):122–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Younes RN et al (2011) Chemotherapy beyond first-line in stage IV metastatic non-small cell lung cancer. Rev Assoc Med Bras (1992) 57(6):686–691

    Article  Google Scholar 

  18. Reck M et al (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung Cancer. N Engl J Med 375(19):1823–1833

    Article  CAS  PubMed  Google Scholar 

  19. D'Alterio C et al (2016) CXCR4-CXCL12-CXCR7, TLR2-TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients. Oncoimmunology 5(12):e1254313

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Sasaki S et al (2018) EBV-associated gastric cancer evades T-cell immunity by PD-1/PD-L1 interactions. Gastric Cancer

  21. Saito H et al (2018) Highly activated PD-1/PD-L1 pathway in gastric Cancer with PD-L1 expression. Anticancer Res 38(1):107–112

    CAS  PubMed  Google Scholar 

  22. Liu S et al (2017) PD-1/PD-L1 interaction up-regulates MDR1/P-gp expression in breast cancer cells via PI3K/AKT and MAPK/ERK pathways. Oncotarget 8(59):99901–99912

    Article  PubMed  PubMed Central  Google Scholar 

  23. Shi W et al (2018) Follicular helper T cells promote the effector functions of CD8(+) T cells via the provision of IL-21, which is downregulated due to PD-1/PD-L1-mediated suppression in colorectal cancer. Exp Cell Res 372(1):35–42

    Article  CAS  PubMed  Google Scholar 

  24. Motzer RJ et al (2015) Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol 33(13):1430–1437

    Article  CAS  PubMed  Google Scholar 

  25. Sharma P, Allison JP (2015) The future of immune checkpoint therapy. Science 348(6230):56–61

    Article  CAS  PubMed  Google Scholar 

  26. Schutz F et al (2017) PD-1/PD-L1 pathway in breast Cancer. Oncol Res Treat 40(5):294–297

    Article  PubMed  CAS  Google Scholar 

  27. Ge Y et al (2013) Blockade of PD-1/PD-L1 immune checkpoint during DC vaccination induces potent protective immunity against breast cancer in hu-SCID mice. Cancer Lett 336(2):253–259

    Article  CAS  PubMed  Google Scholar 

  28. Strickland KC et al (2016) Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget 7(12):13587–13598

    Article  PubMed  PubMed Central  Google Scholar 

  29. Tan D, Sheng L, Yi QH (2018) Correlation of PD-1/PD-L1 polymorphisms and expressions with clinicopathologic features and prognosis of ovarian cancer. Cancer Biomark 21(2):287–297

    Article  CAS  PubMed  Google Scholar 

  30. Powles T et al (2014) MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515(7528):558–562

    Article  CAS  PubMed  Google Scholar 

  31. Kwok G et al (2016) Pembrolizumab (Keytruda). Hum Vaccin Immunother 12(11):2777–2789

    Article  PubMed  PubMed Central  Google Scholar 

  32. Topalian SL et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366(26):2443–2454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hodi FS et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Topalian SL et al (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32(10):1020–1030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bray F et al (2018) Global Cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin

  36. Barlesi F et al (2014) Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed-bevacizumab for advanced nonsquamous nonsmall-cell lung cancer: updated survival analysis of the AVAPERL (MO22089) randomized phase III trial. Ann Oncol 25(5):1044–1052

    Article  CAS  PubMed  Google Scholar 

  37. Ettinger DS et al (2012) Non-small cell lung cancer. J Natl Compr Cancer Netw 10(10):1236–1271

    Article  CAS  Google Scholar 

  38. Shamai S, Merimsky O (2018) Efficacy and safety of Nivolumab in non-small cell lung cancer patients in Tel-Aviv tertiary medical center: facing the reality. Mol Clin Oncol 9(4):419–422

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Osa A et al (2018) Clinical implications of monitoring nivolumab immunokinetics in non-small cell lung cancer patients. JCI Insight:3(19)

  40. Nizam A, Aragon-Ching JB (2018) Frontline immunotherapy treatment with nivolumab and ipilimumab in metastatic renal cell cancer: a new standard of care. Cancer Biol Ther:1–2

  41. Long GV et al (2018) Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol

  42. Hida T (2018) Nivolumab for the treatment of Japanese patients with advanced metastatic non-small cell lung cancer: a review of clinical trial evidence for efficacy and safety. Ther Adv Respir Dis 12:1753466618801167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Grimm SE et al (2018) Nivolumab for treating metastatic or Unresectable urothelial Cancer: An evidence review Group perspective of a NICE single technology appraisal. Pharmacoeconomics

  44. Keir ME et al (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677–704

    Article  CAS  PubMed  Google Scholar 

  45. Agata Y et al (1996) Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol 8(5):765–772

    Article  CAS  PubMed  Google Scholar 

  46. Zaric B et al (2018) PD-1 and PD-L1 protein expression predict survival in completely resected lung adenocarcinoma. Clin Lung Cancer 19:e957–e963

    Article  CAS  PubMed  Google Scholar 

  47. Karim R et al (2009) 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 15(20):6341–6347

    Article  CAS  PubMed  Google Scholar 

  48. PD-1 inhibitors raise survival in NSCLC. Cancer Discov, 2014. 4(1):6

  49. Yang ZZ et al (2015) PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival. Blood Cancer J 5:e281

    Article  PubMed  PubMed Central  Google Scholar 

  50. Prasanth KV, Spector DL (2007) Eukaryotic regulatory RNAs: an answer to the 'genome complexity' conundrum. Genes Dev 21(1):11–42

    Article  CAS  PubMed  Google Scholar 

  51. Enfield KS et al (2012) Mechanistic roles of noncoding RNAs in lung Cancer biology and their clinical implications. Genet Res Int 2012:737416

    PubMed  PubMed Central  Google Scholar 

  52. Mohr AM, Mott JL (2015) Overview of microRNA biology. Semin Liver Dis 35(1):3–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bentwich I et al (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37(7):766–770

    Article  CAS  PubMed  Google Scholar 

  54. Berezikov E et al (2005) Phylogenetic shadowing and computational identification of human microRNA genes. Cell 120(1):21–24

    Article  CAS  PubMed  Google Scholar 

  55. Voorhoeve PM (2010) MicroRNAs: oncogenes, tumor suppressors or master regulators of cancer heterogeneity? Biochim Biophys Acta 1805(1):72–86

    CAS  PubMed  Google Scholar 

  56. Lee YS, Dutta A (2006) MicroRNAs: small but potent oncogenes or tumor suppressors. Curr Opin Investig Drugs 7(6):560–564

    CAS  PubMed  Google Scholar 

  57. Chen CZ (2005) MicroRNAs as oncogenes and tumor suppressors. N Engl J Med 353(17):1768–1771

    Article  CAS  PubMed  Google Scholar 

  58. Ortholan C et al (2009) MicroRNAs and lung cancer: new oncogenes and tumor suppressors, new prognostic factors and potential therapeutic targets. Curr Med Chem 16(9):1047–1061

    Article  CAS  PubMed  Google Scholar 

  59. Wozniak M, Mielczarek A, Czyz M (2016) miRNAs in melanoma: tumor suppressors and oncogenes with prognostic potential. Curr Med Chem 23(28):3136–3153

    Article  CAS  PubMed  Google Scholar 

  60. Bergmann JH, Spector DL (2014) Long non-coding RNAs: modulators of nuclear structure and function. Curr Opin Cell Biol 26:10–18

    Article  CAS  PubMed  Google Scholar 

  61. Cabili MN et al (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25(18):1915–1927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Dinger ME et al (2008) Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res 18(9):1433–1445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Batista PJ, Chang HY (2013) Long noncoding RNAs: cellular address codes in development and disease. Cell 152(6):1298–1307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Pei X, Wang X, Li H (2018) LncRNA SNHG1 regulates the differentiation of Treg cells and affects the immune escape of breast cancer via regulating miR-448/IDO. Int J Biol Macromol 118(Pt A):24–30

    Article  CAS  PubMed  Google Scholar 

  65. Guo Q et al (2015) Comprehensive analysis of lncRNA-mRNA co-expression patterns identifies immune-associated lncRNA biomarkers in ovarian cancer malignant progression. Sci Rep 5:17683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Rusek AM et al (2015) MicroRNA modulators of epigenetic regulation, the tumor microenvironment and the immune system in lung cancer. Mol Cancer 14:34

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Ray M, Ruffalo MM, Bar-Joseph Z (2018) Construction of integrated microRNA and mRNA immune cell signatures to predict survival of patients with breast and ovarian cancer. Genes Chromosom Cancer

  68. Miao BP et al (2015) Nasopharyngeal cancer-derived microRNA-21 promotes immune suppressive B cells. Cell Mol Immunol 12(6):750–756

    Article  CAS  Google Scholar 

  69. Li ZH et al. (2018) MicroRNA-92a promotes tumor growth and suppresses immune function through activation of MAPK/ERK signaling pathway by inhibiting PTEN in mice bearing U14 cervical cancer. Cancer Med

  70. Korsunsky I et al (2017) Two microRNA signatures for malignancy and immune infiltration predict overall survival in advanced epithelial ovarian cancer. J Investig Med 65(7):1068–1076

    Article  PubMed  PubMed Central  Google Scholar 

  71. Khorrami S et al (2017) MicroRNA-146a induces immune suppression and drug-resistant colorectal cancer cells. Tumour Biol 39(5):1010428317698365

    Article  PubMed  CAS  Google Scholar 

  72. Afonso-Grunz F, Muller S (2015) Principles of miRNA-mRNA interactions: beyond sequence complementarity. Cell Mol Life Sci 72(16):3127–3141

    Article  CAS  PubMed  Google Scholar 

  73. Kataoka K et al (2016) Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers. Nature 534(7607):402–406

    Article  CAS  PubMed  Google Scholar 

  74. Du W et al (2017) Variant SNPs at the microRNA complementary site in the B7-H1 3′-untranslated region increase the risk of non-small cell lung cancer. Mol Med Rep 16(3):2682–2690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wang W et al (2012) A frequent somatic mutation in CD274 3'-UTR leads to protein over-expression in gastric cancer by disrupting miR-570 binding. Hum Mutat 33(3):480–484

    Article  CAS  PubMed  Google Scholar 

  76. Gong AY et al (2009) MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes. J Immunol 182(3):1325–1333

    Article  CAS  PubMed  Google Scholar 

  77. Gong AY et al (2010) Cryptosporidium parvum induces B7-H1 expression in cholangiocytes by down-regulating microRNA-513. J Infect Dis 201(1):160–169

    Article  CAS  PubMed  Google Scholar 

  78. Yee D et al (2017) MicroRNA-155 induction via TNF-alpha and IFN-gamma suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells. J Biol Chem 292(50):20683–20693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Zhang J, Braun MY (2014) PD-1 deletion restores susceptibility to experimental autoimmune encephalomyelitis in miR-155-deficient mice. Int Immunol 26(7):407–415

    Article  CAS  PubMed  Google Scholar 

  80. Cioffi M et al (2017) The miR-25-93-106b cluster regulates tumor metastasis and immune evasion via modulation of CXCL12 and PD-L1. Oncotarget 8(13):21609–21625

    Article  PubMed  PubMed Central  Google Scholar 

  81. Takamizawa J et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64(11):3753–3756

    Article  CAS  PubMed  Google Scholar 

  82. Yu SL et al (2008) MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell 13(1):48–57

    Article  CAS  PubMed  Google Scholar 

  83. Wang DT et al (2013) miR-150, p53 protein and relevant miRNAs consist of a regulatory network in NSCLC tumorigenesis. Oncol Rep 30(1):492–498

    Article  PubMed  CAS  Google Scholar 

  84. Fu Y et al (2018) Silencing of Long non-coding RNA MIAT sensitizes lung Cancer cells to Gefitinib by epigenetically regulating miR-34a. Front Pharmacol 9:82

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Shi Y et al (2014) The microRNA miR-34a inhibits non-small cell lung cancer (NSCLC) growth and the CD44hi stem-like NSCLC cells. PLoS One 9(3):e90022

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Wang J et al (2014) Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer. Oncogene 33(9):1181–1189

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Shao Y et al (2016) Direct repression of the oncogene CDK4 by the tumor suppressor miR-486-5p in non-small cell lung cancer. Oncotarget 7(23):34011–34021

    Article  PubMed  PubMed Central  Google Scholar 

  88. Gao ZJ et al (2018) miR-486-5p functions as an oncogene by targeting PTEN in non-small cell lung cancer. Pathol Res Pract 214(5):700–705

    Article  CAS  PubMed  Google Scholar 

  89. Yu S, Geng S, Hu Y (2018) miR-486-5p inhibits cell proliferation and invasion through repressing GAB2 in non-small cell lung cancer. Oncol Lett 16(3):3525–3530

    PubMed  PubMed Central  Google Scholar 

  90. Liang C et al (2017) MicroRNA-18a-5p functions as an oncogene by directly targeting IRF2 in lung cancer. Cell Death Dis 8(5):e2764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Shen Z et al (2015) Effect of miR-18a overexpression on the radiosensitivity of non-small cell lung cancer. Int J Clin Exp Pathol 8(1):643–648

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Chen G et al (2013) miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. PLoS One 8(3):e60317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Park DH et al (2015) MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2. Int J Oncol 47(4):1545–1553

    Article  CAS  PubMed  Google Scholar 

  94. Kapodistrias N, Bobori C, Theocharopoulou G (2017) MiR-140-3p Downregulation in Association with PDL-1 Overexpression in Many Cancers: A Review from the Literature Using Predictive Bioinformatics Tools. Adv Exp Med Biol 988:225–233

    Article  PubMed  Google Scholar 

  95. Ji X, Wang E, Tian F (2018) MicroRNA-140 suppresses osteosarcoma tumor growth by enhancing anti-tumor immune response and blocking mTOR signaling. Biochem Biophys Res Commun 495(1):1342–1348

    Article  CAS  PubMed  Google Scholar 

  96. Xie WB et al (2018) MiR-140 expression regulates cell proliferation and targets PD-L1 in NSCLC. Cell Physiol Biochem 46(2):654–663

    Article  CAS  PubMed  Google Scholar 

  97. Boldrini L et al (2017) Role of microRNA-33a in regulating the expression of PD-1 in lung adenocarcinoma. Cancer Cell Int 17:105

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Jiang D et al (2006) Duplication and expression analysis of multicopy miRNA gene family members in Arabidopsis and rice. Cell Res 16(5):507–518

    Article  CAS  PubMed  Google Scholar 

  99. Senfter D et al (2016) The microRNA-200 family: still much to discover. Biomol Concepts 7(5–6):311–319

    Article  CAS  PubMed  Google Scholar 

  100. Wang R et al (2013) Functional role of miR-34 family in human cancer. Curr Drug Targets 14(10):1185–1191

    Article  CAS  PubMed  Google Scholar 

  101. Vergani E et al (2016) Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b. Oncotarget 7(4):4428–4441

    Article  PubMed  Google Scholar 

  102. Huarte M et al (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142(3):409–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Cortez MA et al (2016) PDL1 Regulation by p53 via miR-34. J Natl Cancer Inst:108(1)

  104. Feng X et al (2014) MiR-200, a new star miRNA in human cancer. Cancer Lett 344(2):166–173

    Article  CAS  PubMed  Google Scholar 

  105. Humphries B, Yang C (2015) The microRNA-200 family: small molecules with novel roles in cancer development, progression and therapy. Oncotarget 6(9):6472–6498

    Article  PubMed  PubMed Central  Google Scholar 

  106. Diaz T et al (2014) Role of miR-200 family members in survival of colorectal cancer patients treated with fluoropyrimidines. J Surg Oncol 109(7):676–683

    Article  CAS  PubMed  Google Scholar 

  107. Chen L et al (2014) Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun 5:5241

    Article  CAS  PubMed  Google Scholar 

  108. Fujita Y et al (2015) The clinical relevance of the miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer. Mol Ther 23(4):717–727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Tang D et al (2018) The miR-3127-5p/p-STAT3 axis up-regulates PD-L1 inducing chemoresistance in non-small-cell lung cancer. J Cell Mol Med 22:3847–3856

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  110. Audrito V et al (2017) PD-L1 up-regulation in melanoma increases disease aggressiveness and is mediated through miR-17-5p. Oncotarget 8(9):15894–15911

    Article  PubMed  PubMed Central  Google Scholar 

  111. Li Q et al (2016) miR-28 modulates exhaustive differentiation of T cells through silencing programmed cell death-1 and regulating cytokine secretion. Oncotarget 7(33):53735–53750

    Article  PubMed  PubMed Central  Google Scholar 

  112. Rivera LB, Bergers G (2013) Location, location, location: macrophage positioning within tumors determines pro- or antitumor activity. Cancer Cell 24(6):687–689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Jahangiri A et al (2013) Gene expression profile identifies tyrosine kinase c-met as a targetable mediator of antiangiogenic therapy resistance. Clin Cancer Res 19(7):1773–1783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Biswas SK, Mantovani A (2010) Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 11(10):889–896

    Article  CAS  PubMed  Google Scholar 

  115. Liu G, Abraham E (2013) MicroRNAs in immune response and macrophage polarization. Arterioscler Thromb Vasc Biol 33(2):170–177

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Choi B et al (2015) The relevance of miRNA-21 in HSV-induced inflammation in a mouse model. Int J Mol Sci 16(4):7413–7427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Zhang G et al (2015) microRNA-4717 differentially interacts with its polymorphic target in the PD1 3′ untranslated region: A mechanism for regulating PD-1 expression and function in HBV-associated liver diseases. Oncotarget 6(22):18933–18944

    Article  PubMed  PubMed Central  Google Scholar 

  118. Zhang Z et al (2008) miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Investig 88(12):1358–1366

    Article  CAS  PubMed  Google Scholar 

  119. Yang SM et al (2013) miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN. Toxicology 306:162–168

    Article  CAS  PubMed  Google Scholar 

  120. Xu Y et al (2012) miR-21 Is a Promising Novel Biomarker for Lymph Node Metastasis in Patients with Gastric Cancer. Gastroenterol Res Pract 2012:640168

    Article  PubMed  PubMed Central  Google Scholar 

  121. P LA et al (2018) Up-Regulation of miR-21, miR-25, miR-93, and miR-106b in Gastric Cancer. Iran Biomed J 22(6):367–373

    Article  Google Scholar 

  122. Zhang H et al (2012) miR-21 downregulated TCF21 to inhibit KISS1 in renal cancer. Urology 80(6):1298–1302 e1

    Article  PubMed  Google Scholar 

  123. An F, Liu Y, Hu Y (2017) miR-21 inhibition of LATS1 promotes proliferation and metastasis of renal cancer cells and tumor stem cell phenotype. Oncol Lett 14(4):4684–4688

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Winther M et al (2015) Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer. Acta Oncol 54(9):1582–1591

    Article  CAS  PubMed  Google Scholar 

  125. Wen SW et al (2015) Association of miR-21 with esophageal cancer prognosis: a meta-analysis. Genet Mol Res 14(2):6578–6582

    Article  CAS  PubMed  Google Scholar 

  126. Fu C et al (2014) The expression of miR-21 and miR-375 predict prognosis of esophageal cancer. Biochem Biophys Res Commun 446(4):1197–1203

    Article  CAS  PubMed  Google Scholar 

  127. Zhang J et al (2012) miR-21, miR-17 and miR-19a induced by phosphatase of regenerating liver-3 promote the proliferation and metastasis of colon cancer. Br J Cancer 107(2):352–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Yu Y et al (2015) miR-21 and miR-145 cooperation in regulation of colon cancer stem cells. Mol Cancer 14:98

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Deng J et al (2014) Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro. Biochem Biophys Res Commun 443(3):789–795

    Article  CAS  PubMed  Google Scholar 

  130. Xue X et al (2016) MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN. Oncotarget 7(51):84508–84519

    Article  PubMed  PubMed Central  Google Scholar 

  131. Xia H et al (2017) miR-21 modulates the effect of EZH2 on the biological behavior of human lung cancer stem cells in vitro. Oncotarget 8(49):85442–85451

    Article  PubMed  PubMed Central  Google Scholar 

  132. Su C et al (2018) MiR-21 improves invasion and migration of drug-resistant lung adenocarcinoma cancer cell and transformation of EMT through targeting HBP1. Cancer Med 7(6):2485–2503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Yang Y, Guo JX, Shao ZQ (2017) miR-21 targets and inhibits tumor suppressor gene PTEN to promote prostate cancer cell proliferation and invasion: An experimental study. Asian Pac J Trop Med 10(1):87–91

    Article  CAS  PubMed  Google Scholar 

  134. Reis ST et al (2012) miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer. BMC Urol 12:14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Amankwah EK et al (2013) miR-21, miR-221 and miR-222 expression and prostate cancer recurrence among obese and non-obese cases. Asian J Androl 15(2):226–230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Zadeh MM, Ranji N, Motamed N (2015) Deregulation of miR-21 and miR-155 and their putative targets after silibinin treatment in T47D breast cancer cells. Iran J Basic Med Sci 18(12):1209–1214

    PubMed  PubMed Central  Google Scholar 

  137. Fragni M et al (2016) The miR-21/PTEN/Akt signaling pathway is involved in the anti-tumoral effects of zoledronic acid in human breast cancer cell lines. Naunyn Schmiedeberg's Arch Pharmacol 389(5):529–538

    Article  CAS  Google Scholar 

  138. Yang CH et al (2015) The oncogenic microRNA-21 inhibits the tumor suppressive activity of FBXO11 to promote tumorigenesis. J Biol Chem 290(10):6037–6046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Iliopoulos D et al (2011) The negative costimulatory molecule PD-1 modulates the balance between immunity and tolerance via miR-21. Eur J Immunol 41(6):1754–1763

    Article  CAS  PubMed  Google Scholar 

  140. Xi J et al (2018) miR-21 depletion in macrophages promotes tumoricidal polarization and enhances PD-1 immunotherapy. Oncogene 37(23):3151–3165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Tran E et al (2015) Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 350(6266):1387–1390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Xie G et al (2017) Helicobacter pylori promote B7-H1 expression by suppressing miR-152 and miR-200b in gastric Cancer cells. PLoS One 12(1):e0168822

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Wang Y et al (2017) MicroRNA-152 regulates immune response via targeting B7-H1 in gastric carcinoma. Oncotarget 8(17):28125–28134

    Article  PubMed  PubMed Central  Google Scholar 

  144. Zhao L et al (2016) The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer. Oncotarget 7(29):45370–45384

    Article  PubMed  PubMed Central  Google Scholar 

  145. Xu C et al (2014) Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer Cell 25(5):590–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Zhu J et al (2014) MiR-20b, −21, and -130b inhibit PTEN expression resulting in B7-H1 over-expression in advanced colorectal cancer. Hum Immunol 75(4):348–353

    Article  CAS  PubMed  Google Scholar 

  147. Shlush LI, Mitchell A (2015) AML evolution from preleukemia to leukemia and relapse. Best Pract Res Clin Haematol 28(2–3):81–89

    Article  PubMed  Google Scholar 

  148. Wang X et al (2015) Tumor suppressor miR-34a targets PD-L1 and functions as a potential immunotherapeutic target in acute myeloid leukemia. Cell Signal 27(3):443–452

    Article  CAS  PubMed  Google Scholar 

  149. Pyzer AR et al (2017) MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs. Leukemia 31(12):2780–2790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Xu S et al (2016) miR-424(322) reverses chemoresistance via T-cell immune response activation by blocking the PD-L1 immune checkpoint. Nat Commun 7:11406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Tao Z et al (2018) MiR-195/−16 family enhances radiotherapy via T cell activation in the tumor microenvironment by blocking the PD-L1 immune checkpoint. Cell Physiol Biochem 48(2):801–814

    Article  CAS  PubMed  Google Scholar 

  152. Huang F et al (2018) MicroRNA-374b inhibits liver cancer progression via down regulating programmed cell death-1 expression on cytokine-induced killer cells. Oncol Lett 15(4):4797–4804

    PubMed  PubMed Central  Google Scholar 

  153. Wu Q et al (2018) miR-375 inhibits IFN-gamma-induced programmed death 1 ligand 1 surface expression in head and neck squamous cell carcinoma cells by blocking JAK2/STAT1 signaling. Oncol Rep 39(3):1461–1468

    CAS  PubMed  Google Scholar 

  154. Wei J et al (2016) MiR-138 exerts anti-glioma efficacy by targeting immune checkpoints. Neuro-Oncology 18(5):639–648

    Article  CAS  PubMed  Google Scholar 

  155. Jia L et al (2017) miR-142-5p regulates tumor cell PD-L1 expression and enhances anti-tumor immunity. Biochem Biophys Res Commun 488(2):425–431

    Article  CAS  PubMed  Google Scholar 

  156. Zou MX et al (2018) Clinicopathologic implications of CD8(+)/Foxp3(+) ratio and miR-574-3p/PD-L1 axis in spinal chordoma patients. Cancer Immunol Immunother 67(2):209–224

    Article  CAS  PubMed  Google Scholar 

  157. He B, Yan F, Wu C (2018) Overexpressed miR-195 attenuated immune escape of diffuse large B-cell lymphoma by targeting PD-L1. Biomed Pharmacother 98:95–101

    Article  CAS  PubMed  Google Scholar 

  158. Gao L et al (2019) MiR-873/PD-L1 axis regulates the stemness of breast cancer cells. EBioMedicine 41:395–407

    Article  PubMed  PubMed Central  Google Scholar 

  159. Tang Y et al (2017) Co-expression of AFAP1-AS1 and PD-1 predicts poor prognosis in nasopharyngeal carcinoma. Oncotarget 8(24):39001–39011

    Article  PubMed  PubMed Central  Google Scholar 

  160. Haderk F et al (2017) Tumor-derived exosomes modulate PD-L1 expression in monocytes. Science Immunology 2(13)

    Article  PubMed  Google Scholar 

  161. Zhang C et al (2019) Upregulation of long noncoding RNA SNHG20 promotes cell growth and metastasis in esophageal squamous cell carcinoma via modulating ATM-JAK-PD-L1 pathway. J Cell Biochem

  162. Gilligan KE, Dwyer RM (2017) Engineering Exosomes for Cancer Therapy. Int J Mol Sci:18(6)

  163. Kazandjian D et al (2016) FDA approval summary: Nivolumab for the treatment of metastatic non-small cell lung Cancer with progression on or after platinum-based chemotherapy. Oncologist 21(5):634–642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Tanaka K et al. (2013) Tumor-suppressive function of protein-tyrosine phosphatase non-receptor type 23 in testicular germ cell tumors is lost upon overexpression of miR142-3p microRNA. J Biol Chem 288(33): p. 23990-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Our work is supported by The National Natural Science Foundation of China grants 81572122 to Shanghai Sixth People’s Hospital, affiliated to Shanghai Jiao Tong University.

Funding

The National Natural Science Foundation of China (81572122).

Author information

Authors and Affiliations

  1. Lab for Noncoding RNA & Cancer, School of Life Science, Shanghai University, Shanghai, 200444, China

    Lei Ding & Yanli Li

  2. Shanghai Sixth People’s Hospital, affiliated to Shanghai Jiao Tong University, Shanghai, 200233, China

    Shengdi Lu

Authors
  1. Lei Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shengdi Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yanli Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Data collection and analysis, manuscript writing: L-D. Funding Supporter: SD-L. Manuscript revision and supervision: SD-L, YL-L.

Corresponding authors

Correspondence to Shengdi Lu or Yanli Li.

Ethics declarations

Ethical Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

There is no conflict of interest regarding this article.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ding, L., Lu, S. & Li, Y. Regulation of PD-1/PD-L1 Pathway in Cancer by Noncoding RNAs. Pathol. Oncol. Res. 26, 651–663 (2020). https://doi.org/10.1007/s12253-019-00735-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-019-00735-9

Keywords

Search

Navigation