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Comparison of PD-L1 and VISTA expression status in primary and recurrent/refractory tissue after (chemo)radiotherapy in head and neck cancer

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Abstract

Background

PD-L1 and VISTA are thought to play a role in escape from the immune system, tumor progression, and treatment response in tumoral tissue. The current study aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on PD-L1 and VISTA expression in head and neck cancers.

Methods

PD-L1 and VISTA expression were compared between the primary biopsy taken at the time of diagnosis and refractory tissue biopsies of patients who received definitive CRT or recurrent tissue biopsies of patients who had surgery followed by adjuvant RT or CRT.

Results

In total, 47 patients were included. Radiotherapy had no effect on the expression levels of PD-L1 and VISTA in patients with head and neck cancer (p = 0.542 and p = 0.425, respectively). A positive correlation was found between PD-L1 and VISTA expression (p < 0.001; r = 0.560). PD-L1 and VISTA expression in the first biopsy were found to be significantly higher in clinical lymph node-positive patients compared to node-negative patients (PD-L1 p = 0.038; VISTA p = 0.018). The median overall survival of patients with ≥ 1% VISTA expression in the initial biopsy was significantly shorter than that of patients with < 1% VISTA expression (52.4 vs. 110.1 months, respectively; p = 0.048).

Conclusion

It was found that PD-L1 and VISTA expression did not change with RT or CRT. Further studies are needed to evaluate the relationship of PD-L1 and VISTA expression with RT and CRT.

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References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics, 2021. CA Cancer J Clin 71(1):7–33. https://doi.org/10.3322/caac.21654

    Article  PubMed  Google Scholar 

  2. Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ et al (2019) The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer 7(1):184. https://doi.org/10.1186/s40425-019-0662-5

    Article  PubMed Central  PubMed  Google Scholar 

  3. Cognetti DM, Weber RS, Lai SY (2008) Head and neck cancer: an evolving treatment paradigm. Cancer 113(7):1911–1932. https://doi.org/10.1002/cncr.23654

    Article  PubMed  Google Scholar 

  4. Havel JJ, Chowell D, Chan TA (2019) The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer 19(3):133–150. https://doi.org/10.1038/s41568-019-0116-x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Gibney GT, Weiner LM, Atkins MB (2016) Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol 17(12):e542–e51. https://doi.org/10.1016/s1470-2045(16)30406-5

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Maleki Vareki S, Garrigós C, Duran I (2017) Biomarkers of response to PD-1/PD-L1 inhibition. Crit Rev Oncol Hematol 116:116–124. https://doi.org/10.1016/j.critrevonc.2017.06.001

    Article  PubMed  Google Scholar 

  7. Cramer JD, Burtness B, Ferris RL (2019) Immunotherapy for head and neck cancer: recent advances and future directions. Oral Oncol 99:104460. https://doi.org/10.1016/j.oraloncology.2019.104460

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Nowak EC, Lines JL, Varn FS, Deng J, Sarde A, Mabaera R et al (2017) Immunoregulatory functions of VISTA. Immunol Rev 276(1):66–79. https://doi.org/10.1111/imr.12525

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8(6):467–477. https://doi.org/10.1038/nri2326

    Article  CAS  PubMed  Google Scholar 

  10. Tagliamento M, Bironzo P, Novello S (2020) New emerging targets in cancer immunotherapy: the role of VISTA. ESMO Open 4(3):e683. https://doi.org/10.1136/esmoopen-2020-000683

    Article  PubMed Central  PubMed  Google Scholar 

  11. Huang X, Zhang X, Li E, Zhang G, Wang X, Tang T et al (2020) VISTA: an immune regulatory protein checking tumor and immune cells in cancer immunotherapy. J Hematol Oncol 13(1):83. https://doi.org/10.1186/s13045-020-00917-y

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Zhu AX, Finn RS, Ikeda M, Sung MW, Baron AD, Kudo M et al (2020) A phase Ib study of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC). American Society of Clinical Oncology

    Book  Google Scholar 

  13. Makowska A, Meier S, Shen L, Busson P, Baloche V, Kontny U (2021) Anti-PD‑1 antibody increases NK cell cytotoxicity towards nasopharyngeal carcinoma cells in the context of chemotherapy-induced upregulation of PD‑1 and PD-L1. Cancer Immunol Immunother 70(2):323–336. https://doi.org/10.1007/s00262-020-02681-x

    Article  CAS  PubMed  Google Scholar 

  14. Tran L, Allen CT, Xiao R, Moore E, Davis R, Park SJ et al (2017) Cisplatin alters antitumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinoma. Cancer Immunol Res 5(12):1141–1151. https://doi.org/10.1158/2326-6066.Cir-17-0235

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Demaria S, Golden EB, Formenti SC (2015) Role of local radiation therapy in cancer immunotherapy. JAMA Oncol 1(9):1325–1332. https://doi.org/10.1001/jamaoncol.2015.2756

    Article  PubMed  Google Scholar 

  16. Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC et al (2009) Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA‑4 antibody. Clin Cancer Res 15(17):5379–5388. https://doi.org/10.1158/1078-0432.Ccr-09-0265

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Buchwald ZS, Wynne J, Nasti TH, Zhu S, Mourad WF, Yan W et al (2018) Radiation, immune checkpoint blockade and the abscopal effect: a critical review on timing, dose and fractionation. Front Oncol 8:612. https://doi.org/10.3389/fonc.2018.00612

    Article  PubMed Central  PubMed  Google Scholar 

  18. Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867. https://doi.org/10.1056/NEJMoa1602252

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ et al (2019) Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 393(10167):156–167. https://doi.org/10.1016/s0140-6736(18)31999-8

    Article  CAS  PubMed  Google Scholar 

  20. Bahleda R, Braiteh F, Balmanoukian A, Braña I, Hodi F, Garbo L et al (2017) Long-term safety and clinical outcomes of atezolizumab in head and neck cancer: phase Ia trial results. Ann Oncol 28:v373

    Article  Google Scholar 

  21. Katsuya Y, Horinouchi H, Asao T, Kitahara S, Goto Y, Kanda S et al (2016) Expression of programmed death 1 (PD-1) and its ligand (PD-L1) in thymic epithelial tumors: Impact on treatment efficacy and alteration in expression after chemotherapy. Lung Cancer 99:4–10. https://doi.org/10.1016/j.lungcan.2016.05.007

    Article  PubMed  Google Scholar 

  22. Pilones KA, Hensler M, Daviaud C, Kraynak J, Fucikova J, Galluzzi L et al (2020) Converging focal radiation and immunotherapy in a preclinical model of triple negative breast cancer: contribution of VISTA blockade. OncoImmunology 9(1):1830524. https://doi.org/10.1080/2162402x.2020.1830524

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. van den Ende T, van den Boorn HG, Hoonhout NM, van Etten-Jamaludin FS, Meijer SL, Derks S et al (2020) Priming the tumor immune microenvironment with chemo(radio)therapy: a systematic review across tumor types. Biochim Biophys Acta Rev Cancer 1874(1):188386. https://doi.org/10.1016/j.bbcan.2020.188386

    Article  CAS  PubMed  Google Scholar 

  24. Gong J, Le TQ, Massarelli E, Hendifar AE, Tuli R (2018) Radiation therapy and PD-1/PD-L1 blockade: the clinical development of an evolving anticancer combination. J Immunother Cancer 6(1):46. https://doi.org/10.1186/s40425-018-0361-7

    Article  PubMed Central  PubMed  Google Scholar 

  25. Wang Y, Kim TH, Fouladdel S, Zhang Z, Soni P, Qin A et al (2019) PD-L1 expression in circulating tumor cells increases during radio(chemo)therapy and indicates poor prognosis in non-small cell lung cancer. Sci Rep 9(1):566. https://doi.org/10.1038/s41598-018-36096-7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Oweida A, Lennon S, Calame D, Korpela S, Bhatia S, Sharma J et al (2017) Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma. OncoImmunology 6(10):e1356153. https://doi.org/10.1080/2162402x.2017.1356153

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Hecht M, Büttner-Herold M, Erlenbach-Wünsch K, Haderlein M, Croner R, Grützmann R et al (2016) PD-L1 is upregulated by radiochemotherapy in rectal adenocarcinoma patients and associated with a favourable prognosis. Eur J Cancer 65:52–60. https://doi.org/10.1016/j.ejca .2016.06.015

    Article  CAS  PubMed  Google Scholar 

  28. Patel KR, Martinez A, Stahl JM, Logan SJ, Perricone AJ, Ferris MJ et al (2018) Increase in PD-L1 expression after pre-operative radiotherapy for soft tissue sarcoma. OncoImmunology 7(7):e1442168

    Article  PubMed Central  PubMed  Google Scholar 

  29. Yoneda K, Kuwata T, Kanayama M, Mori M, Kawanami T, Yatera K et al (2019) Alteration in tumoural PD-L1 expression and stromal CD8-positive tumour-infiltrating lymphocytes after concurrent chemo-radiotherapy for non-small cell lung cancer. Br J Cancer 121(6):490–496. https://doi.org/10.1038/s41416-019-0541-3

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Qian JM, Schoenfeld JD (2020) Radiotherapy and immunotherapy for head and neck cancer: current evidence and challenges. Front Oncol 10:608772. https://doi.org/10.3389/fonc.2020.608772

    Article  PubMed  Google Scholar 

  31. Schoop H, Bregenzer A, Halske C, Behrens HM, Krüger S, Egberts JH et al (2020) Therapy resistance in neoadjuvantly treated gastric cancer and cancer of the gastroesophageal junction is associated with an increased expression of immune checkpoint inhibitors-comparison against a therapy naïve cohort. Transl Oncol 13(2):165–176. https://doi.org/10.1016/j.tranon.2019.11.004

    Article  PubMed  Google Scholar 

  32. McBride S, Sherman E, Tsai CJ, Baxi S, Aghalar J, Eng J et al (2021) Randomized phase II trial of nivolumab with stereotactic body radiotherapy versus nivolumab alone in metastatic head and neck squamous cell carcinoma. J Clin Oncol 39(1):30–37. https://doi.org/10.1200/jco.20.00290

    Article  CAS  PubMed  Google Scholar 

  33. Theelen W, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts J et al (2019) Effect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non-small cell lung cancer: results of the PEMBRO-RT phase 2 randomized clinical trial. JAMA Oncol 5(9):1276–1282. https://doi.org/10.1001/jamaoncol.2019.1478

    Article  PubMed Central  PubMed  Google Scholar 

  34. Patel SP, Kurzrock R (2015) PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 14(4):847–856. https://doi.org/10.1158/1535-7163.Mct-14-0983

    Article  CAS  PubMed  Google Scholar 

  35. Downes MR, Slodkowska E, Katabi N, Jungbluth AA, Xu B (2020) Inter- and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma. Histopathology 76(2):191–200. https://doi.org/10.1111/his.13946

    Article  PubMed  Google Scholar 

  36. Rasmussen JH, Lelkaitis G, Håkansson K, Vogelius IR, Johannesen HH, Fischer BM et al (2019) Intratumor heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma. Br J Cancer 120(10):1003–1006. https://doi.org/10.1038/s41416-019-0449-y

    Article  PubMed Central  PubMed  Google Scholar 

  37. Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G Jr. et al (2019) Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet 394(10212):1915–1928. https://doi.org/10.1016/s0140-6736(19)32591-7

    Article  CAS  PubMed  Google Scholar 

  38. Liu J, Yuan Y, Chen W, Putra J, Suriawinata AA, Schenk AD et al (2015) Immune-checkpoint proteins VISTA and PD‑1 nonredundantly regulate murine T‑cell responses. Proc Natl Acad Sci U S A 112(21):6682–6687. https://doi.org/10.1073/pnas.1420370112

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Kakavand H, Jackett LA, Menzies AM, Gide TN, Carlino MS, Saw RPM et al (2017) Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD‑1 therapy in metastatic melanoma patients. Mod Pathol 30(12):1666–1676. https://doi.org/10.1038/modpathol.2017.89

    Article  CAS  PubMed  Google Scholar 

  40. Wu L, Deng WW, Huang CF, Bu LL, Yu GT, Mao L et al (2017) Expression of VISTA correlated with immunosuppression and synergized with CD8 to predict survival in human oral squamous cell carcinoma. Cancer Immunol Immunother 66(5):627–636. https://doi.org/10.1007/s00262-017-1968-0

    Article  CAS  PubMed  Google Scholar 

  41. Zhang M, Pang H‑J, Zhao W, Li Y‑F, Yan L‑X, Dong Z‑Y et al (2018) VISTA expression associated with CD8 confers a favorable immune microenvironment and better overall survival in hepatocellular carcinoma. BMC Cancer 18(1):1–8

    Google Scholar 

  42. Zong L, Zhou Y, Zhang M, Chen J, Xiang Y (2020) VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer. Cancer Immunol Immunother 69(1):33–42. https://doi.org/10.1007/s00262-019-02434-5

    Article  CAS  PubMed  Google Scholar 

  43. Cao X, Ren X, Zhou Y, Mao F, Lin Y, Wu H et al (2020) VISTA expression on immune cells correlates with favorable prognosis in patients with triple-negative breast cancer. Front Oncol 10:583966. https://doi.org/10.3389/fonc.2020.583966

    Article  PubMed  Google Scholar 

  44. Vassilakopoulou M, Avgeris M, Velcheti V, Kotoula V, Rampias T, Chatzopoulos K et al (2016) Evaluation of PD-L1 expression and associated tumor-infiltrating lymphocytes in laryngeal squamous cell carcinoma. Clin Cancer Res 22(3):704–713. https://doi.org/10.1158/1078-0432.Ccr-15-1543

    Article  CAS  PubMed  Google Scholar 

  45. Lin YM, Sung WW, Hsieh MJ, Tsai SC, Lai HW, Yang SM et al (2015) High PD-L1 expression correlates with metastasis and poor prognosis in oral squamous cell carcinoma. PLoS ONE 10(11):e142656. https://doi.org/10.1371/journal.pone.0142656

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Liao H, Zhu H, Liu S, Wang H (2018) Expression of V‑domain immunoglobulin suppressor of T cell activation is associated with the advanced stage and presence of lymph node metastasis in ovarian cancer. Oncol Lett 16(3):3465–3472. https://doi.org/10.3892/ol.2018.9059

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Yang WF, Wong MCM, Thomson PJ, Li KY, Su YX (2018) The prognostic role of PD-L1 expression for survival in head and neck squamous cell carcinoma: a systematic review and meta-analysis. Oral Oncol 86:81–90. https://doi.org/10.1016/j.oraloncology.2018.09.016

    Article  CAS  PubMed  Google Scholar 

  48. Tang H, Zhou X, Ye Y, Zhou Y, Wu C, Xu Y (2020) The different role of PD-L1 in head and neck squamous cell carcinomas: a meta-analysis. Pathol Res Pract 216(1):152768. https://doi.org/10.1016/j.prp.2019.152768

    Article  CAS  PubMed  Google Scholar 

  49. Bauml J, Seiwert TY, Pfister DG, Worden F, Liu SV, Gilbert J et al (2017) Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: results from a single-arm, phase II study. J Clin Oncol 35(14):1542–1549. https://doi.org/10.1200/jco.2016.70.1524

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Ferris RL, Blumenschein G Jr., Fayette J, Guigay J, Colevas AD, Licitra L et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867. https://doi.org/10.1056/NEJMoa1602252

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Mehra R, Seiwert TY, Gupta S, Weiss J, Gluck I, Eder JP et al (2018) Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. Br J Cancer 119(2):153–159. https://doi.org/10.1038/s41416-018-0131-9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Aydil U, Akmansu M, Gümüşay Ö, Eravcı FC, Bakkal FK, Yazıcı Ö et al (2019) Failure of concurrent chemoradiotherapy for organ preservation in laryngeal cancer: survival outcomes and recurrence patterns. Ear Nose Throat J 98(7):E92–e6. https://doi.org/10.1177/0145561319839788

    Article  PubMed  Google Scholar 

  53. Agra IM, Ferlito A, Takes RP, Silver CE, Olsen KD, Stoeckli SJ et al (2012) Diagnosis and treatment of recurrent laryngeal cancer following initial nonsurgical therapy. Head Neck 34(5):727–735. https://doi.org/10.1002/hed.21739

    Article  PubMed  Google Scholar 

  54. Esteller E, Vega MC, López M, Quer M, León X (2011) Salvage surgery after locoregional failure in head and neck carcinoma patients treated with chemoradiotherapy. Eur Arch Otorhinolaryngol 268(2):295–301. https://doi.org/10.1007/s00405-010-1365-1

    Article  CAS  PubMed  Google Scholar 

  55. León X, Quer M, Orús C, López M, Gras JR, Vega M (2001) Results of salvage surgery for local or regional recurrence after larynx preservation with induction chemotherapy and radiotherapy. Head Neck 23(9):733–738. https://doi.org/10.1002/hed.1104

    Article  PubMed  Google Scholar 

  56. Birkeland AC, Beesley L, Bellile E, Rosko AJ, Hoesli R, Chinn SB et al (2017) Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma. Head Neck 39(12):2512–2518. https://doi.org/10.1002/hed.24918

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgements

This study was supported by the Gazi University Projects of Scientific Investigation.

Funding

The authors received no specific funding for this work. This study was carried out as part of the Project Support program of the Gazi University Projects of Scientific Investigation.

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Authors and Affiliations

Authors

Contributions

All authors contributed to study conception and design. Material preparation, data collection, and analysis were performed by Görkem Yazıcı Şener, Osman Sütcüoğlu, Betül Öğüt, Nalan Akyürek, and Ozan Yazıcı. The first draft of the manuscript was written by Osman Sütcüoğlu, Görkem Yazıcı Şener, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Osman Sütcüoğlu MD.

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Conflict of interest

G.Y. Şener, O. Sütcüoğlu, B. Öğüt, D.C. Güven, A. Kavuncuoğlu, N. Özdemir, A. Özet, S. Aksoy, Y.G.G. Tezel, N. Akyürek, and O. Yazıcı declare that they have no competing interests.

Ethical standards

Ethical approval was waived by the Ethics Committee of Gazi University in view of the retrospective nature of the study and all the procedures performed were part of the routine care.

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Availability of data and material

The datasets generated during and/or analyzed in the current study are available from the corresponding author upon reasonable request.

Appendix

Appendix

 

Table 4 PD-L1 and VISTA expression according to lymph node status
Table 5 PD-L1 and VISTA expression according to archival period
Table 6 PD-L1 and VISTA change by treatment group
Table 7 Treatments applied at the time of diagnosis
Fig. 4
figure 4

Microscopic view of PD-L1 expression change before and after treatment. PD-L1 expression before therapy (abc) and after therapy (def). Decreased expression of PD-L1 with treatment; the patient’s pretreatment PD-L1 score was 3 (a) and posttreatment PD-L1 score was 0 (d). Increased expression of PD-L1 with treatment; the patient’s pretreatment PD-L1 score was 0 (b) and the posttreatment PD-L1 score was 2 (e). The group with no change in PD-L1 expression; PD-L1 score before and after treatment 2 (cf). PD-L1 programmed death-ligand 1

Fig. 5
figure 5

Microscopic view of VISTA expression change before and after treatment. VISTA expression levels before therapy (a, b, c) and after therapy (def). Increase in VISTA expression with treatment; the patient had a pretreatment VISTA score of 0 (a) and a posttreatment VISTA score of 2 (d). Group with no change in VISTA expression; the patient had a pretreatment VISTA score of 2 (b) and a posttreatment VISTA score of 2 (e). Decreased VISTA expression; the patient with a VISTA score of 2 (c) has a VISTA score of 0 (f) after treatment. VISTA V-domain Ig suppressor of T cell activation

Fig. 6
figure 6

Second biopsy PD-L1 expression and overall survival. PD-L1 programmed death-ligand 1

Fig. 7
figure 7

Second biopsy VISTA expression and overall survival. VISTA V-domain Ig suppressor of T cell activation

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Şener, G.Y., Sütcüoğlu, O., Öğüt, B. et al. Comparison of PD-L1 and VISTA expression status in primary and recurrent/refractory tissue after (chemo)radiotherapy in head and neck cancer. Strahlenther Onkol 199, 761–772 (2023). https://doi.org/10.1007/s00066-023-02053-1

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