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-alpha, IL-7R alpha) 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.
[1]Jilin Univ, Hosp 1, Dept Gynecol Oncol, Changchun 130061, Jilin, Peoples R China.
[2]Jilin Univ, Hosp 1, Dept Canc Immunol, Changchun 130061, Jilin, Peoples R China.
[3]Jilin Univ, China Japan Union Hosp, Dept Rheumatol & Immunol, Changchun 130033, Jilin, Peoples R China.
[4]Jilin Univ, Hosp 1, Dept Hematol, Changchun 130061, Jilin, Peoples R China.
[5]Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA.
(8.0+极速模式)