title: Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study.
abstract: OBJECTIVE
  Tumor infiltrating lymphocytes (TILs) in the microenvironment reflect may tumor biology and predict outcome. We previously demonstrated that infiltrates of CD4, CD8, and FoxP3 positive lymphocytes were associated with HPV-status and survival in oropharyngeal cancers. To determine if TILs were of prognostic importance in oral cancer, TIL levels were evaluated retrospectively in 52 oral cancer patients treated with surgery and correlations with outcome determined.
  
  
  METHODS
  Complete TIL and clinical data were available for 39 patients. Levels of CD4, CD8, FoxP3 (Treg), CD68 and NK cells were assessed by immunohistochemistry in tumor cores on a tissue microarray. Associations with clinical variables, tobacco and alcohol use and histologic features were assessed using Spearman correlation coefficient and the non-parametric Kruskal-Wallis testing. Time-to-event outcomes were determined using univariate and multivariate Cox models. Median follow up was 60 months.
  
  
  RESULTS
  The ratio of CD4/CD8 (p=.01) and CD8 infiltrates (p=.05) were associated with tumor recurrence but not overall survival. Lower CD4 infiltrates were associated with alcohol use (p=.005) and poor tumor differentiation (p=.02). Interestingly, higher levels of CD68+ macrophages were found associated with positive nodes (p=.06) and poorer overall survival (p=.07). Overall and DSS survival were significantly shorter for patients with positive nodes, extracapsular spread, or perineural invasion.
  
  
  CONCLUSIONS
  Infiltrating immune cell levels in oral cavity cancer appear influenced by health behaviors and tumor characteristics. In contrast to oropharynx cancer, infiltrates of CD68 positive tumor associated macrophages may contribute to metastatic behavior and outcome in advanced oral cavity carcinoma.
authors.affiliation: Departments of Otolaryngology-Head and Neck Surgery, The University of Michigan Health System, Ann Arbor, MI 48109, United States. Electronic address: gregwolf@umich.edu.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.affiliation: Departments of Otolaryngology-Head and Neck Surgery, The University of Michigan Health System, Ann Arbor, MI 48109, United States.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.affiliation: Biostatistics, The University of Michigan Health System, Ann Arbor, MI 48109, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Bellile
authors.affiliation: Departments of Otolaryngology-Head and Neck Surgery, The University of Michigan Health System, Ann Arbor, MI 48109, United States.
authors.forename: Ariane
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Pathology, The University of Michigan Health System, Ann Arbor, MI 48109, United States.
authors.forename: Daffyd
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Pathology, The University of Michigan Health System, Ann Arbor, MI 48109, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McHugh
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000276:immunology*; D011379:Prognosis
keywords: Oral cavity cancer; Tumor associated macrophage; Tumor infiltrating lymphocytes