IL-33 drives the antitumor effects of dendritic cells via the induction of Tc9 cells

Ning Liu, Yuxue Jiang, Jintong Chen, He Nan, Yinghua Zhao, Xiao Chu, Alison Wang, Dongjiao Wang, Tianxue Qin, Sujun Gao, Qing Yi, Ying Yue, Siqing Wang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalCellular and Molecular Immunology
DOIs
StateE-pub ahead of print - Oct 1 2018

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