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Int J Cancer. 2016 Jan 1;138(1):171-81. doi: 10.1002/ijc.29683. Epub 2015 Jul 30.

CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG).

Balermpas P1,2, Rödel F1,2, Rödel C1,2, Krause M3,4,5,6, Linge A3,4,5, Lohaus F3,4,5, Baumann M3,4,5,6, Tinhofer I7,8, Budach V7,8, Gkika E9,10, Stuschke M9,10, Avlar M11,12, Grosu AL11,12, Abdollahi A13,14, Debus J13,14, Bayer C15, Stangl S15, Belka C15,16, Pigorsch S15,17, Multhoff G15,17, Combs SE15,17, Mönnich D18,19, Zips D18,19, Fokas E1,2.

Author information

1
German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Frankfurt, Germany.
2
Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Germany.
3
German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Dresden, Germany.
4
Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
5
OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
6
Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology, Germany.
7
German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Berlin, Germany.
8
Department of Radiooncology and Radiotherapy, Charité-University Hospital Berlin, Germany.
9
German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Essen, Germany.
10
Department of Radiotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
11
German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Freiburg, Germany.
12
Department of Radiation Oncology, University of Freiburg, Germany.
13
German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Heidelberg, Germany.
14
Department of Radiation Oncology, Heidelberg Ion Therapy Center (HIT), Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany.
15
German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Munich, Germany.
16
Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-University, Munich, Germany.
17
Department of Radiation Oncology, Technical University Munich, Germany.
18
German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Tübingen, Germany.
19
Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen, Eberhard Karls University Tübingen, Germany.

Abstract

We examined the prognostic value of tumour-infiltrating lymphocytes (TILs) in patients with squamous cell carcinoma of the head and neck (SCCHN) after surgery and postoperative cisplatin-based chemoradiotherapy. FFPE-tissue originating from the surgery of 161 patients treated in 8 DKTK partner sites was immunohistochemically stained for CD3 and CD8. Their expression was correlated with clinicopathological characteristics as well as overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of the HPV16-DNA/p16 status. After a median follow-up of 48 months (range: 4100 months), OS at 4 years was 46.5% for the entire cohort. In multivariate analysis, high CD8 expression was confirmed as an independent prognostic parameter for OS (p = 0.002), LPFS (p = 0.004) and DMFS (p = 0.006), while CD3 expression lacked significance. In multivariate analysis HPV16 DNA positivity was associated with improved OS (p = 0.025) and LPFS (p = 0.013) and p16-positive patients showed improved DMFS (p = 0.008). Interestingly, high CD8 expression was a prognostic parameter for the clinical outcome in both HPV16 DNA-positive and HPV16 DNA-negative patients. Similar findings were observed in the multivariate analysis for the combined HPV16 DNA/p16 status. Altogether, CD8+ TILs constitute an independent prognostic marker in SCCHN patients treated with adjuvant chemoradiotherapy. These data indicate that CD8-positive TILs have antitumour activity and could be used for treatment stratification. Further validation of the prognostic value of CD8+ TILs as a biomarker and its role in the immune response in SCCHN patients after adjuvant chemoradiotherapy is warranted and will be performed in the prospective DKTK-ROG study.

KEYWORDS:

CD8; DKTK-ROG; HPV; SCCHN; postoperative chemoradiotherapy; prognostic

PMID:
26178914
DOI:
10.1002/ijc.29683
[Indexed for MEDLINE]
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