IL-10 in vitro could enhance IFNγ expression and suppress PD-1 expression in CD8 T cells from esophageal cancer patients

Abstract

IL-10 is commonly regarded as an immunoregulatory cytokine, but accumulating evidence suggests that IL-10 may promote CD8 T cell expansion and proliferation. In this study, tumor infiltrating (TI) and peripheral blood (PB) CD8 T cells were collected from esophageal cancer patients. Interestingly, IL-10 concentration in the tumor microenvironment increased with advancing tumor stage, while TI CD8 T cell-mediated IL-10 production decreased with advancing tumor stage. By flow cytometry, three distinctive subsets, including IL-10+IFNγ−, IL-10+IFNγ+, and IL-10−IFNγ+, could be observed in TI CD8 T cells. The former two subsets were present at much higher frequency in stage I and stage II patients than in stage III patients. IL-10+IFNγ+ TI CD8 T cells presented significantly higher IFNγ and lower PD-1 expression than the IL-10−IFNγ+ TI CD8 T cells. PB CD8 T cells, on the other hand, produced little IL-10 but potent IFNγ upon stimulation. Interestingly, intermediate level of exogenous IL-10 could significantly elevate the expression of IFNγ by PB CD8 T cells, while high level of exogenous IL-10 resulted in reduced expression of IFNγ by PB CD8 T cells. Exogenous IL-10 could not significantly reduce the frequencies of PD-1+ PB CD8 T cells, but significantly reduced the MFI of PD-1 in the PB CD8 T cells, especially in stage III patients. Together, this investigation demonstrated that IL-10 enhanced IFNγ expression and suppressed PD-1 expression in PB and TI CD8 T cells; however, the frequency of IL-10-expressing TI CD8 T cells decreased with increasing severity in esophageal cancer.