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

Yifan Chu; Jing Liao; Jinqing Li; Yongchun Wang; Xingjuan Yu; Junfeng Wang; Xiue Xu; Liyan Xu; Limin Zheng; Jing Xu; Lian Li

doi:10.7150/jca.30354

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

J Cancer. 2019 Aug 28;10(21):5234-5243. doi: 10.7150/jca.30354. eCollection 2019.

Authors

Yifan Chu¹, Jing Liao², Jinqing Li¹, Yongchun Wang¹, Xingjuan Yu¹, Junfeng Wang¹, Xiue Xu³, Liyan Xu³, Limin Zheng^{1

2}, Jing Xu¹, Lian Li²

Affiliations

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.

Abstract

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: CD103; esophageal squamous cell carcinoma; prognosis; tumor-infiltrating lymphocytes.