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).
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.
['Balermpas|Panagiotis|P|', 'Rödel|Franz|F|', 'Rödel|Claus|C|', 'Krause|Mechthild|M|', 'Linge|Annett|A|', 'Lohaus|Fabian|F|', 'Baumann|Michael|M|', 'Tinhofer|Inge|I|', 'Budach|Volker|V|', 'Gkika|Eleni|E|', 'Stuschke|Martin|M|', 'Avlar|Melanie|M|', 'Grosu|Anca-Lidia|AL|', 'Abdollahi|Amir|A|', 'Debus|Jürgen|J|', 'Bayer|Christine|C|', 'Stangl|Stefan|S|', 'Belka|Claus|C|', 'Pigorsch|Steffi|S|', 'Multhoff|Gabriele|G|', 'Combs|Stephanie E|SE|', 'Mönnich|David|D|', 'Zips|Daniel|D|', 'Fokas|Emmanouil|E|http://orcid.org/0000-0003-1601-6165']
D000328:Adult D000368:Aged D000971:Antineoplastic Combined Chemotherapy Protocols D014408:Biomarkers, Tumor D018414:CD8-Positive T-Lymphocytes D002294:Carcinoma, Squamous Cell D004279:DNA, Viral D005260:Female D006258:Head and Neck Neoplasms D006801:Humans D016130:Immunophenotyping D016246:Lymphocytes, Tumor-Infiltrating D008297:Male D008875:Middle Aged D060787:Neoplasm Grading D009367:Neoplasm Staging D027383:Papillomaviridae D030361:Papillomavirus Infections D010641:Phenotype D011182:Postoperative Care D011379:Prognosis D000077195:Squamous Cell Carcinoma of Head and Neck D016896:Treatment Outcome D014412:Tumor Virus Infections
CD8 HPV postoperative chemoradiotherapy DKTK-ROG prognostic SCCHN