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)

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

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • DNA, Viral
  • Female
  • Head and Neck Neoplasms / etiology*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy
  • Humans
  • Immunophenotyping
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Papillomaviridae* / genetics
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / virology*
  • Phenotype
  • Postoperative Care
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck
  • Treatment Outcome
  • Tumor Virus Infections / complications
  • Tumor Virus Infections / virology*

Substances

  • Biomarkers, Tumor
  • DNA, Viral