The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).

Balermpas, Panagiotis; Rödel, Franz; Krause, Mechthild; Linge, Annett; Lohaus, Fabian; Baumann, Michael; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Gkika, Eleni; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Stangl, Stefan; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Multhoff, Gabriele; Combs, Stephanie E; Welz, Stefan; Zips, Daniel; Lim, Su Yin; Rödel, Claus; Fokas, Emmanouil

doi:10.1002/ijc.30770

2017

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Titel:: The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).
Dokumenttyp:: Journal Article
Autor(en):: Balermpas, Panagiotis; Rödel, Franz; Krause, Mechthild; Linge, Annett; Lohaus, Fabian; Baumann, Michael; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Gkika, Eleni; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Stangl, Stefan; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Multhoff, Gabriele; Combs, Stephanie E; Welz, Stefan; Zips, Daniel; Lim, Su Yin; Rödel, Claus; Fokas, Emmanouil
Abstract:: We examined the prognostic role of PD-1+ and CD8+ tumor infiltrating lymphocytes (TILs), and PD-L1+ cells in patients with squamous cell carcinoma of the head and neck (SCCHN) treated with surgery and postoperative chemoradiotherapy (CRT). FFPE samples from 161 patients were immunohistochemically stained for PD-1, CD8 and PD-L1. The immune marker expression was correlated with clinicopathologic characteristics, and overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of HPV16 DNA/p16 status. The median follow-up was 48 months (range: 4-100). The 2-year-OS was 84.1% for the entire cohort. High PD-1 and PD-L1 expression were more common in patients with positive HPV16 DNA (p < 0.001 and p = 0.008, respectively) and high infiltration by CD8+ TILs (p < 0.001 for both markers). High PD-L1 expression correlated with superior OS (p = 0.025), LPFS (p = 0.047) and DMFS (p = 0.048) in multivariable analysis, whereas no significance could be demonstrated for PD-1. Patients with CD8high /PD-L1high expression had favorable outcome (p < 0.001 for all endpoints) compared to other groups. We validated the superior OS data on CD8high /PD-L1high using the Cancer Genome Atlas TCGA dataset (n = 518; p = 0.032). High PD-L1 expression was a favorable prognostic marker in HPV16-negative but not HPV16-positive patients. In conclusion, HPV-positive tumors showed higher expression of immune markers. PD-L1 expression constitutes an independent prognostic marker in SCCHN patients post-adjuvant CRT. In conjunction with CD8 status, these data provide an important insight on the immune contexture of SCCHN and are directly relevant for future treatment stratification with PD-1/PD-L1 immune checkpoint inhibitors to complement CRT.
Zeitschriftentitel:: Int J Cancer
Jahr:: 2017
Band / Volume:: 141
Heft / Issue:: 3
Seitenangaben Beitrag:: 594-603
Sprache:: eng
Volltext / DOI:: doi:10.1002/ijc.30770
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/28480996
Print-ISSN:: 0020-7136
TUM Einrichtung:: Klinik und Poliklinik für RadioOnkologie und Strahlentherapie
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für RadioOnkologie und Strahlentherapie (Prof. Combs)2017