Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma

Oncotarget. 2017 Feb 21;8(8):13762-13769. doi: 10.18632/oncotarget.14632.

Abstract

CD103 is the αE subunit of αEβ7 integrin that is expressed in tissue-resident memory T cells, where it promotes cytotoxic T cell responses against tumors. However, little is known about its expression or clinicopathological implications in non-small cell lung cancer (NSCLC). This study investigated the prognostic implications of CD103+ tumor-infiltrating lymphocytes (TILs) in NSCLC. We established two cohorts: patients with resected NSCLC (n = 132) and patients with pulmonary squamous cell carcinoma (pSCC), a subset of NSCLC (n = 378), to estimate the prognostic significance of CD103+ TILs. The numbers of CD103+ TILs in the intratumoral (i.e., intraepithelial) and stromal regions of NSCLC were estimated using immunohistochemistry and automated image analysis. In the NSCLC cohort, high numbers of intratumoral CD103+ TILs were significantly associated with prolonged disease-free survival (DFS) and overall survival (OS) in patients with pSCC but not in those with pulmonary adenocarcinoma. In the pSCC cohort, a positive correlation was observed between the numbers of intratumoral CD103+ and CD8+ TILs (correlation coefficient = 0.736, P < 0.001). The ratio of intratumoral/stromal CD103+ TILs was higher in pSCC with high compared to low E-cadherin expression (P = 0.021). According to Kaplan-Meier analysis, high intratumoral but not stromal CD103+ TILs were associated with prolonged DFS and OS in patients with resected pSCC (P = 0.021 and 0.002, respectively). Multivariate analysis revealed that a high number of intratumoral CD103+ TILs is an independent predictor of a more favorable DFS (P = 0.021). Thus, a high number of intratumoral CD103+ TILs is a favorable prognostic indicator in patients with pSCC.

Keywords: CD103; cancer immunotherapy; prognosis; pulmonary squamous cell carcinoma; tumor-infiltrating lymphocytes.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Integrin alpha Chains / biosynthesis
  • Integrin alpha Chains / immunology
  • Kaplan-Meier Estimate
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • T-Lymphocyte Subsets / immunology*
  • Tissue Array Analysis

Substances

  • Antigens, CD
  • Integrin alpha Chains
  • alpha E integrins