| Autor: |
Zhao, Bao, Gong, Weipeng, Ma, Anjun, Chen, Jianwen, Velegraki, Maria, Dong, Hong, Liu, Zihao, Wang, Lingling, Okimoto, Tamio, Jones, Devin M., Lei, Yu L., Long, Meixiao, Oestreich, Kenneth J., Ma, Qin, Xin, Gang, Carbone, David P., He, Kai, Li, Zihai, Wen, Haitao |
| Zdroj: |
Nature Immunology; November 2022, Vol. 23 Issue: 11 p1588-1599, 12p |
| Abstrakt: |
Dysfunctional CD8+T cells, which have defective production of antitumor effectors, represent a major mediator of immunosuppression in the tumor microenvironment. Here, we show that SUSD2 is a negative regulator of CD8+T cell antitumor function. Susd2−/−effector CD8+T cells showed enhanced production of antitumor molecules, which consequently blunted tumor growth in multiple syngeneic mouse tumor models. Through a quantitative mass spectrometry assay, we found that SUSD2 interacted with interleukin (IL)-2 receptor α through sushi domain-dependent protein interactions and that this interaction suppressed the binding of IL-2, an essential cytokine for the effector functions of CD8+T cells, to IL-2 receptor α. SUSD2 was not expressed on regulatory CD4+T cells and did not affect the inhibitory function of these cells. Adoptive transfer of Susd2−/−chimeric antigen receptor T cells induced a robust antitumor response in mice, highlighting the potential of SUSD2 as an immunotherapy target for cancer. |
| Databáze: |
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