Gastric cancer patients display a distinctive population of IFNg⁺IL10⁺ double positive CD8 T cells, which persists longer during prolonged activation

IL10 is generally regarded as a broad-spectrum regulatory cytokine. However, the role of IL10 in CD8 T cells remains controversial. In this study, we investigated the characteristics of endogenous IL10 by CD8 T cells in gastric cancer (GC) patients. Using intracellular staining, we found that in both GC patients and healthy controls, the majority of IL10-expressing CD8 T cells also presented concurrent IFNg expression. Interestingly, the frequency of IFNg⁺IL10⁺ CD8 T cells was significantly higher in GC patients than in healthy controls, while the frequency of IFNg⁺IL10^- CD8 T cells was significantly lower in GC patients than in healthy controls. Compared to the IFNg^-IL10^- CD8 T cells, both IFNg⁺IL10^- and IFNg⁺IL10⁺ CD8 T cells presented significantly higher expression of activation/inhibitory markers. Interestingly, the IFNg⁺IL10⁺ cells presented lower PD1 and TIM3 and higher KLRG1 than the IFNg⁺IL10^- CD8 T cells. Remarkably, the IFNg⁺IL10⁺ CD8 T cells, but not the IFNg⁺IL10^- CD8 T cells, were highly enriched in the CD45RO⁺CXCR5⁺ subset. Prolonged activation resulted in significant enrichment of IFNg⁺IL10⁺ CD8 T cells over time. Interestingly, compared to the CD45RO⁺CXCR5^- CD8 T cells, the CD45RO⁺CXCR5⁺ CD8 T cells presented stronger proliferation capacity at later stages of stimulation, and higher viability throughout the stimulation process. Overall, our investigation demonstrated that GC patients were enriched with a distinctive population of IFNg⁺IL10⁺ double positive CD8 T cells, which resembled T follicular cytotoxic cells and could persist longer during prolonged activation.