Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103(+)CD8(+) T cells conferring favourable prognosis

Li, RC; Liu, H; Cao, YF; Wang, JT; Chen, YF; Qi, YY; Lv, KP; Liu, X; Yu, K; Lin, C; Zhang, H; He, HY; Li, H; Chen, LL; Shen, ZB; Qin, J; Zhang, WJ; Sun, YH; Xu, JJ

Sun, YH (corresponding author), Fudan Univ, Zhongshan Hosp, Dept Gen Surg, Shanghai, Peoples R China.; Zhang, WJ (corresponding author), Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai, Peoples R China.; Xu, JJ (corresponding author), Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Shanghai, Peoples R China.

BRITISH JOURNAL OF CANCER, 2020; 122 (10): 1525

Abstract

Background Intratumoural CD103(+)CD8(+) T cells have been linked to prolonged survival in several malignancies. However, the clinical significance of CD103(+)CD8(+) T cells in gastric cancer remains unexplored. Methods Gastric cancer tissues from Zhongshan Hospital and data from Gene Expression Omnibus were obtained and analysed. Immunohistochemistry and flow cytometry were performed to detect the number and phenotypical characteristics of CD103(+)CD8(+) T cells. The effect of programmed cell death protein-1 (PD-1) blockade on CD103(+)CD8(+) T cells was evaluated with the use of an in vitro study based on fresh tumour tissues. Results CD103(+)CD8(+) T cells predicted superior overall survival and provided better prognostic power than total CD8(+) T cells in gastric cancer. Patients with high CD103(+)CD8(+) T cell infiltration also gained more benefit from adjuvant chemotherapy. Flow cytometry analysis showed that CD103(+)CD8(+) T cells exerted superior anti-tumour effects with stronger retention capacity and cytotoxicity. Moreover, an in vitro study showed that CD103(+)CD8(+) T cells were more functionally restored after PD-1 blockade than CD103(-)CD8(+) T cells. Conclusions CD103(+)CD8(+) T cells might be a useful marker to predict prognosis and therapeutic efficacy for gastric cancer patients. Efforts to increase intratumoural CD103(+)CD8(+) T cell frequency might be a novel therapeutic strategy in gastric cancer.

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