IL-35 expression correlated with the decrease in T cell cytotoxicity and T cell exhaustion
Published reports have indicated that IL-35 induces tumor tolerance and evasion mainly through an increase in Tregs frequency or function, but decreased cytotoxic T cell function [9, 12, 13]. We then compared the level of Foxp3 expression, the main transcription factor of Tregs; the level of expression was significantly associated with IL-35 content (Fig.5A). Similarly, the level of IL-10 expression in the IL-35 high sample group was significantly higher than the IL-35 low expression group (Fig.5B). Hacohen et al. (17) developed a quantitative measure of the activity of tumor-infiltrating lymphocytes, especially CD8+T cells, based on two key effector genes (GZMA and PRF1), referred to as cytolytic activity (CYT). We demonstrated that the “CYT” significantly decreased in the IL-35 high group sample and there was less IFN-γ expressed (Fig.5C and D), which indicated impaired cytotoxic immunity. Furthermore, we detected the expression of some T cell exhaustion markers and found that PD1 and LAG3 were positively correlated with the IL-35 level, which showed a significant increase in the IL-35 high expression group (Fig.5E and F).