细胞生物学
CD8型
生物
细胞毒性T细胞
效应器
癌症免疫疗法
T细胞
嵌合抗原受体
过继性细胞移植
细胞因子
白细胞介素2受体
免疫疗法
免疫系统
癌症研究
免疫学
生物化学
体外
作者
Bao Zhao,Weipeng Gong,Anjun Ma,Jianwen Chen,Maria Velegraki,Hong Dong,Zihao Liu,Lingling Wang,Tamio Okimoto,Devin M. Jones,Yu L. Lei,Meixiao Long,Kenneth J. Oestreich,Qin Ma,Gang Xin,David P. Carbone,Kai He,Zihai Li,Haitao Wen
出处
期刊:Nature Immunology
[Nature Portfolio]
日期:2022-10-20
卷期号:23 (11): 1588-1599
被引量:19
标识
DOI:10.1038/s41590-022-01326-8
摘要
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. Wen and colleagues show that the transmembrane protein SUSD2 is a specific negative regulator of CD8+ T cells activation in the tumor environment by interacting with IL-2 receptor α and interfering with IL-2 binding to the receptor.
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