title: 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).
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.
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Frankfurt, Germany.|Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Germany.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Balermpas
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Frankfurt, Germany.|Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Rödel
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Frankfurt, Germany.|Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Dresden, Germany.|Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.|OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.|Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology, Germany.
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Dresden, Germany.|Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.|OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Linge
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Dresden, Germany.|Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.|OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Lohaus
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Dresden, Germany.|Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.|OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.|Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Berlin, Germany.|Department of Radiooncology and Radiotherapy, Charité-University Hospital Berlin, Germany.
authors.forename: Inge
authors.initials: I
authors.lastname: Tinhofer
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Berlin, Germany.|Department of Radiooncology and Radiotherapy, Charité-University Hospital Berlin, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Budach
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Essen, Germany.|Department of Radiotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Eleni
authors.initials: E
authors.lastname: Gkika
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Essen, Germany.|Department of Radiotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stuschke
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Freiburg, Germany.|Department of Radiation Oncology, University of Freiburg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Avlar
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Freiburg, Germany.|Department of Radiation Oncology, University of Freiburg, Germany.
authors.forename: Anca-Lidia
authors.initials: AL
authors.lastname: Grosu
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Heidelberg, Germany.|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.
authors.forename: Amir
authors.initials: A
authors.lastname: Abdollahi
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Heidelberg, Germany.|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.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Bayer
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stangl
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Munich, Germany.|Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Belka
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Munich, Germany.|Department of Radiation Oncology, Technical University Munich, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Pigorsch
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Munich, Germany.|Department of Radiation Oncology, Technical University Munich, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Multhoff
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Munich, Germany.|Department of Radiation Oncology, Technical University Munich, Germany.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Combs
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Tübingen, Germany.|Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen, Eberhard Karls University Tübingen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Mönnich
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Tübingen, Germany.|Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen, Eberhard Karls University Tübingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg Germany and German Cancer Consortium (DKTK), Frankfurt, Germany.|Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Germany.
authors.forename: Emmanouil
authors.identifier: http://orcid.org/0000-0003-1601-6165
authors.initials: E
authors.lastname: Fokas
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D004279:DNA, Viral; D005260:Female; D006258:Head and Neck Neoplasms / Q000209:etiology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology*; D010641:Phenotype; D011182:Postoperative Care; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000150:complications / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral
keywords: CD8; DKTK-ROG; HPV; SCCHN; postoperative chemoradiotherapy; prognostic