Research Papers:
Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma
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Abstract
Jaemoon Koh1,2, Sehui Kim1, Moon-Young Kim3, Heounjeong Go4, Yoon Kyung Jeon1,5,*, Doo Hyun Chung1,2,6,*
1Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
3Department of Forensic Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
4Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
5Tumor Immunity Medical Research Center, Tumor Microenvironment Global Core Research Center, Cancer Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
6Ischemic/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: [email protected]
Yoon Kyung Jeon, email: [email protected]
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 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.
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