title: Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma.
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.
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jaemoon
authors.initials: J
authors.lastname: Koh
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sehui
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Forensic Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Moon-Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Heounjeong
authors.initials: H
authors.lastname: Go
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.|Tumor Immunity Medical Research Center, Tumor Microenvironment Global Core Research Center, Cancer Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.|Ischemic/Hypoxia Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000473:pathology; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000096:biosynthesis / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D046888:Tissue Array Analysis
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; C091367:alpha E integrins
keywords: CD103; cancer immunotherapy; prognosis; pulmonary squamous cell carcinoma; tumor-infiltrating lymphocytes