論文

査読有り 国際誌
2019年10月15日

Endogenous IL-33 exerts CD8+ T cell antitumor responses overcoming pro-tumor effects by regulatory T cells in a colon carcinoma model.

Biochemical and biophysical research communications
  • Yulong Xia
  • ,
  • Tatsukuni Ohno
  • ,
  • Naoto Nishii
  • ,
  • Arundhati Bhingare
  • ,
  • Hidetake Tachinami
  • ,
  • Yoshihisa Kashima
  • ,
  • Shigenori Nagai
  • ,
  • Hirohisa Saito
  • ,
  • Susumu Nakae
  • ,
  • Miyuki Azuma

518
2
開始ページ
331
終了ページ
336
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2019.08.058

Interleukin-33 (IL-33) is a nuclear-associated cytokine of the IL-1 family. IL-33 and its receptor ST2 axis exert conflicting anti-tumor and pro-tumor effects in various tumors. In this study, we examined the role of endogenously produced IL-33 in the colon-26 tumor model, in which involvement of the IL-33:ST2 pathway was negligible on the tumor side. We found that the generation of regulatory T cells (Tregs) and CD8+ T cells, and IFN-γ expression by both CD4+ and CD8+ T cells (T cell activation) were impaired in IL-33-deficient mice. Overall antitumor responses, assessed by tumor growth and IFN-γ expression by tumor-infiltrating CD8+ T cells, were also impaired, even after Treg adjustment prior to tumor inoculation. These results indicate that endogenous IL-33 augmented CD8+ T cell-mediated antitumor responses in this colon carcinoma model, with higher CD8+ T cell-infiltration and overcoming pro-tumor effects by increased Tregs. Exogenous application of IL-33 into the tumors did not enhance CD8+ T cell-mediated antitumor responses despite marked elevation of innate responses showing upregulation of proinflammatory cytokine/chemokine expression, neutrophil recruitment, and dendritic cell activation. Our results suggest a dual role for endogenous IL-33 in antitumor responses and suggest that the balance of CD8+ T cells:Tregs in the tumor microenvironment is one of key factors for estimating the contribution of IL-33-mediated antitumor responses. Therefore, the development of IL-33-based cancer immunotherapy may require a target cell-specific approach.

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2019.08.058
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31421832

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