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Endogenous IL-33 exerts CD8+ T cell antitumor responses overcoming pro-tumor effects by regulatory T cells in a colon carcinoma model.
- Source :
-
Biochemical & Biophysical Research Communications . Oct2019, Vol. 518 Issue 2, p331-336. 6p. - Publication Year :
- 2019
-
Abstract
- 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. • IL-33 deficiency reduces generation of CD8+ T cells and regulatory T cells. • Antitumor responses to colon-26 tumor is impaired in IL-33 deficient mice. • Tumor-recruiting CD8+ T cells and Tregs are impaired in IL-33KO mice. • Endogenous IL-33 promotes CD8+ T cells and Tregs with opposite function. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 518
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 138415658
- Full Text :
- https://doi.org/10.1016/j.bbrc.2019.08.058