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

Cellular & Molecular Immunology (2018) | Download Citation

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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.

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Acknowledgements

This work was supported by funds from National Natural Science Foundation of China (81372536 to S.W., 81502452 to X.C. and 81602485 to Y.Z.).

Author information

Affiliations

  1. Department of Gynecological Oncology, The First Hospital of Jilin University, Changchun, 130061, China

    • Ning Liu
    • , Dongjiao Wang
    •  & Ying Yue
  2. Department of Cancer Immunology, The First Hospital of Jilin University, Changchun, 130061, China

    • Yuxue Jiang
    • , Jintong Chen
    • , Yinghua Zhao
    • , Xiao Chu
    • , Alison Wang
    • , Qing Yi
    •  & Siqing Wang
  3. Department of Rheumatology and Immunology, China-Japan Union Hospital of Jilin University, Changchun, 130033, China

    • He Nan
  4. Department of Hematology, The First Hospital of Jilin University, Changchun, 130061, China

    • Tianxue Qin
    •  & Sujun Gao
  5. Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA

    • Qing Yi

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Contributions

S.W. and Y.Y. initiated the study. S.W. designed the experiments and wrote the paper. S.W., N.L., Y.J., J.C., H.N, Y.Z., X.C., A.W., D.W. and T.Q. performed the experiments and statistical analyses. A.W. read and edited the manuscript. Q.Y. and S.G. provided critical suggestions to this study.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Ying Yue or Siqing Wang.

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DOI

https://doi.org/10.1038/s41423-018-0166-0