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

Abstract

CD103 is the α _E subunit of α _Eβ ₇ 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.