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

// Jaemoon Koh 1, 2 , Sehui Kim 1 , Moon-Young Kim 3 , Heounjeong Go 4 , Yoon Kyung Jeon 1, 5, * , Doo Hyun Chung 1, 2, 6, * 1 Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea 2 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea 3 Department of Forensic Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea 4 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea 5 Tumor Immunity Medical Research Center, Tumor Microenvironment Global Core Research Center, Cancer Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea 6 Ischemic/Hypoxia Institute, Seoul National University College of Medicine, Seoul, Republic of Korea * These authors contributed equally to this work Correspondence to: Doo Hyun Chung, email: doohyun@snu.ac.kr Yoon Kyung Jeon, email: junarplus@chol.com Keywords: CD103, tumor-infiltrating lymphocytes, pulmonary squamous cell carcinoma, prognosis, cancer immunotherapy Received: August 01, 2016      Accepted: January 06, 2017      Published: January 13, 2017 ABSTRACT CD103 is the α E subunit of α E β 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.