| First Author | Xia Y | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 518 |
| Issue | 2 | Pages | 331-336 |
| PubMed ID | 31421832 | Mgi Jnum | J:291421 |
| Mgi Id | MGI:6444033 | Doi | 10.1016/j.bbrc.2019.08.058 |
| Citation | Xia Y, et al. (2019) Endogenous IL-33 exerts CD8(+) T cell antitumor responses overcoming pro-tumor effects by regulatory T cells in a colon carcinoma model. Biochem Biophys Res Commun 518(2):331-336 |
| abstractText | 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-gamma 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-gamma 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. |
