J Cancer 2019; 10(21):5234-5243. doi:10.7150/jca.30354 This issue

Research Paper

CD103+ tumor-infiltrating lymphocytes predict favorable prognosis in patients with esophageal squamous cell carcinoma

Yifan Chu1*, Jing Liao2*, Jinqing Li1, Yongchun Wang1, Xingjuan Yu1, Junfeng Wang1, Xiue Xu3, Liyan Xu3, Limin Zheng1,2, Jing Xu1✉, Lian Li2✉

1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
2. MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P. R. China
3. The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Chu Y, Liao J, Li J, Wang Y, Yu X, Wang J, Xu X, Xu L, Zheng L, Xu J, Li L. CD103+ tumor-infiltrating lymphocytes predict favorable prognosis in patients with esophageal squamous cell carcinoma. J Cancer 2019; 10(21):5234-5243. doi:10.7150/jca.30354. Available from https://www.jcancer.org/v10p5234.htm

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As an indispensable factor in preventing the recirculation of tissue lymphocytes to the lymphatic and blood systems, the integrin CD103 has enabled the characterization of lymphocyte populations in non-lymphoid tissues and organs. However, the expression, distribution, and clinical significance of CD103+ tumor-infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) remain unclear. In the present study, we included tumor and adjacent non-tumor tissue specimens from 198 patients with ESCC who had undergone surgical resection. Immunohistochemistry and immunofluorescence were used to detect CD103+ TIL distribution, as well as the co-expression of CD103 and T cell markers and functional molecules. Kaplan-Meier analysis and the Cox proportional hazards model were used to estimate the prognostic value of CD103+ TILs. The results showed that CD103+ TILs were predominantly located in adjacent non-tumor tissues compared with tumor tissues (P < 0.0001). Immunofluorescence double staining revealed that CD8+ T cells, but not CD4+ T cells, comprised the majority of CD103-expressing cells. Most of these CD103-expressing cells co-expressed CTLA-4 and granzyme B rather than the exhaustion marker PD-1. High density of intratumoral CD103+ TIL is associated with longer overall survival (OS) and disease-free survival (DFS) in both the internal (OS, P = 0.0004 and DFS, P = 0.0002) and external (OS, P = 0.038 and DFS, P = 0.12) cohorts. Multivariate Cox analysis showed the density of CD103+ TILs was an independent positive prognostic factor for OS (hazards ratio [HR] = 0.406; P = 0.0003 in the internal cohort; HR = 0.328, P = 0.01, in the external cohort) and DFS (HR = 0.385; P = 0.0002 in the internal cohort; HR = 0.270, P = 0.003, in the external cohort). Our findings indicate that CD103+ TILs might play an important role in the tumor microenvironment, and intratumoral CD103+ TILs could serve as a promising prognostic marker in ESCC.

Keywords: esophageal squamous cell carcinoma, prognosis, CD103, tumor-infiltrating lymphocytes