Tumor-infiltrating CD226+CD8+ T cells are associated with postoperative prognosis and adjuvant chemotherapeutic benefits in gastric cancer patients

Purpose Defining the phenotypic characteristics of CD8(+)T cell subsets in gastric cancer (GC) can help remodel the immune microenvironment of the tumor, thereby improving patient prognosis. CD226 has recently been shown to regulate the activity of CD8(+)T cell in several malignancies. However, the clinical relevance of CD226(+)CD8(+)T cells in GC remains unclear. Methods Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 316), The Cancer Genome Atlas (TCGA) cohort (n = 407), KUGH/KUCM cohort (n = 202), and Asian Cancer Research Group (ACRG) cohort (n = 300) were included in prognosis and response to adjuvant chemotherapy (ACT) analyses. Flow cytometry and multiplex immunostaining were used to characterize CD226(+)CD8(+)T cells. Results CD226(+)CD8(+)T cells predicted favorable outcomes in patients undergoing curative resection for GC. GC patients with high CD226(+)CD8(+)T cell infiltration benefitted more from adjuvant chemotherapy. CD155 is upregulated in GC tissues and is associated with decreased intra-tumoral CD226(+)CD8(+)T cell infiltration. The combination of intra-tumoral CD226(+)CD8(+)T cells and CD155 is a strong prognostic predictor in patients with GC. Conclusion CD226(+)CD8(+)T cells may represent a novel therapeutic target and a useful marker of prognosis and therapeutic response in patients with GC.