摘要
Dendritic cell(DC)tumor vaccines exert their antitumor effects through the induction of effector T cells.We recently identified Tc9 cells as a new potent antitumor effector T cell subset.However,approaches to direct DCs to preferably prime antitumor Tc9 cells should be further exploited.Here,we demonstrate that the addition of interleukin(IL)-33 potently promotes the induction of Tc9 cells by DCs in vitro and in vivo.IL-33 treatment also drives the cytotoxic activities of DC-induced Tc9 cells.Notably,IL-33 treatment enhances cell survival and proliferation of DC-primed CD8+T cells.More importantly,the addition of IL-33 during in vitro priming of tumor-specific Tc9 cells by DCs increases the antitumor capability of Tc9 cells.Mechanistic studies demonstrated that IL-33 treatment inhibits exhaustive CD8+T cell differentiation by inhibiting PD-1 and 2B4 expression and increasing IL-2 and CD127(IL-7 receptor-α,IL-7Rα)expression in CD8+T cells.Finally,the addition of IL-33 further promotes the therapeutic efficacy of DC-based tumor vaccines in the OT-I mouse model.Our study demonstrates the important role of IL-33 in DC-induced Tc9 cell differentiation and antitumor immunity and may have important clinical implications.
基金
funds from National Natural Science Foundation of China(81372536 to S.W.,81502452 to X.C.and 81602485 to Y.Z.).
