Intratumoral PD-1(+)CD8(+) T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer

BACKGROUND: Although PD-1 has been reported to be a marker of T-cell exhaustion in several malignancies, the biological role of PD-1(+)CD8(+) T cells in gastric cancer (GC) remains unclear. Herein, we aimed to investigate the role of PD-1(+)CD8(+) T cells in the tumour microenvironment and its clinical significance in GC. DESIGNS: This study included 441 tumour microarray specimens and 60 Flow cytometry specimens of GC patients from Zhongshan Hospital, and 250 GC patients from the Asian Cancer Research Group. RESULTS: Here, we demonstrated that PD-1(+)CD8(+) T cells functioned as an independent adverse prognosticator in GC. In addition, an abundance of intratumoral PD-1(+)CD8(+) T cells indicated worse chemotherapeutic responsiveness to fluorouracil in Stage III GC patients. Mechanistically, PD-1(+)CD8(+) T cell high infiltration indicated an exhausted phenotype of global CD8(+) T cells in GC tissues, which was characterised by elevated immune checkpoint expression including CTLA-4 and TIM-3, whereas decreased expression of perforin. Furthermore, PD-1(+)CD8(+) T cell high-infiltration patients with Stage III GC held elevated activity of several therapeutic signal pathways. CONCLUSIONS: Our study highlighted that PD-1(+)CD8(+) T cell abundance predicts inferior prognosis in GC, and may serve as a novel predictive biomarker to guide therapeutic option.