CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
SUSD2 通过靶向 IL-2 受体信号抑制 CD8(+) T 细胞抗肿瘤免疫
英文原题：SUSD2 suppresses CD8(+) T cell antitumor immunity by targeting IL-2 receptor signaling.
查看英文原题
SUSD2 suppresses CD8(+) T cell antitumor immunity by targeting IL-2 receptor signaling.
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中文摘要
功能失调的CD8+ T细胞，其抗肿瘤效应分子产生存在缺陷，是肿瘤微环境中免疫抑制的主要介导者。在此，我们发现SUSD2是CD8+ T细胞抗肿瘤功能的负调控因子。Susd2-/-效应CD8+ T细胞显示出抗肿瘤分子产生增强，从而在多种同系小鼠肿瘤模型中减缓了肿瘤生长。通过定量质谱分析，我们发现SUSD2通过sushi结构域依赖性蛋白相互作用与白细胞介素（IL）-2受体α相互作用，并且这种相互作用抑制了IL-2（一种对CD8+ T细胞效应功能至关重要的细胞因子）与IL-2受体α的结合。SUSD2不在调节性CD4+ T细胞上表达，也不影响这些细胞的抑制功能。过继转移Susd2-/-CAR-T 细胞在小鼠中诱导了强大的抗肿瘤反应，突显了SUSD2作为癌症免疫治疗靶点的潜力。
展开英文摘要原文
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.
论文信息
- 作者
- Zhao B、Gong W、Ma A、Chen J、Velegraki M、Dong H、Liu Z、Wang L
- 第一作者单位
- Department of Microbial Infection and Immunity, Infectious Disease Institute, The Ohio State University, Columbus, OH, USA.United States
- 通讯作者单位
- Department of Microbial Infection and Immunity, Infectious Disease Institute, The Ohio State University, Columbus, OH, USA. Haitao.Wen@osumc.edu.United States
- 文献类型
- 非美国政府资助研究 · 美国 NIH 资助研究
- 期刊
- Nature immunology2022 Nov
- 原文标识
- PubMed 36266363 · DOI 10.1038/s41590-022-01326-8
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