title: Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer.
abstract: BACKGROUND
  We aimed to investigate the prognostic value of tumour-infiltrating lymphocytes' (TILs) expression in pretreatment specimens from patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT).
  
  
  METHODS
  The prevalence of CD3+, CD8+, CD4+ and FOXP3+ TILs was assessed using immunohistochemistry in tumour tissue obtained from 101 patients before CRT and was correlated with clinicopathological characteristics as well as local failure-free- (LFFS), distant metastases free- (DMFS), progression-free (PFS) and overall survival (OS). Survival curves were measured using the Kaplan-Meier method, and differences in survival between the groups were estimated using the log-rank test. Prognostic effects of TIL subset density were determined using the Cox regression analysis.
  
  
  RESULTS
  With a mean follow-up of 25 months (range, 2.3-63 months), OS at 2 years was 57.4% for the entire cohort. Patients with high immunohistochemical CD3 and CD8 expression had significantly increased OS (P=0.024 and P=0.028), PFS (P=0.044 and P=0.047) and DMFS (P=0.021 and P=0.026) but not LFFS (P=0.90 and P=0.104) in multivariate analysis that included predictive clinicopathologic factors, such as age, sex, T-stage, N-stage, tumour grading and localisation. Neither CD4 nor FOXP3 expression showed significance for the clinical outcome. The lower N-stage was associated with improved OS in the multivariate analysis (P=0.049).
  
  
  CONCLUSIONS
  The positive correlation between a high number of infiltrating CD3+ and CD8+ cells and clinical outcome indicates that TILs may have a beneficial role in HNSCC patients and may serve as a biomarker to identify patients likely to benefit from definitive CRT.
authors.affiliation: Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Balermpas
authors.affiliation: Senckenberg Institute of Pathology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Michel
authors.forename: J
authors.initials: J
authors.lastname: Wagenblast
authors.affiliation: Department of Maxillofacial Surgery, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Seitz
authors.affiliation: Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Weiss
authors.affiliation: Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Rödel
authors.affiliation: Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rödel
authors.affiliation: Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Fokas
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000628:therapy*; D059248:Chemoradiotherapy; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck