Inhibition of the cancer stem cell immune checkpoint SOAT1 suppresses regulatory T cell functions through a trans-cellular 20(S)-Hydroxycholesterol-GPR132 pathway in mice

	Inhibition of the cancer stem cell immune checkpoint SOAT1 suppresses regulatory T cell functions through a trans-cellular 20(S)-Hydroxycholesterol-GPR132 pathway in mice
	Ding, YH; Fang, WQ; Xiang, RQ; Liu, HT; Huang, ML; Shen, YR; Chen, Y; Wang, GH; Zhou, ZC; Ling, Y; Sun, LV; Wang, YT; Hou, SX
	2026
发表期刊	Nat. Commun.
卷号	17 期号:1
摘要	Although cancer immunotherapy has recently revolutionized treatment, the low response rate to existing immune checkpoint blockade (ICB) underscores the need for new druggable targets. Here, we find that SOAT1 is selectively expressed in cancer stem cell (CSC) and pharmacological inhibition with STK results in robust anti-tumor effects across various preclinical mouse models, including colon, liver, lung, breast, and melanoma cancer, with low toxicity. Mechanistically, treatment with STK (or gene knockdown of Soat1) induces the release of 20(S)-Hydroxycholesterol (20SOHC) from the tumor cells, and downstream activation of the trans-cellular 20SOHC (tumor)- GPR132 pathway in regulatory T cell (Treg), ultimately resulting in the suppression of Treg functions and enhanced dendritic cells and cytotoxic CD8+ T cell responses. Importantly, STK treatment synergizes with anti-PD-1 or anti-CTLA-4 ICB therapy. Thus, our findings identify SOAT1 as a CSC metabolism checkpoint that facilitates immune evasion and SOAT1 inhibition as a promising strategy for advanced cancer immunotherapy.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/15029
专题	科研部门_脑疾病遗传与机理（王国昊）
推荐引用方式 GB/T 7714	Ding, YH,Fang, WQ,Xiang, RQ,et al. Inhibition of the cancer stem cell immune checkpoint SOAT1 suppresses regulatory T cell functions through a trans-cellular 20(S)-Hydroxycholesterol-GPR132 pathway in mice[J]. Nat. Commun.,2026,17(1).
APA	Ding, YH.,Fang, WQ.,Xiang, RQ.,Liu, HT.,Huang, ML.,...&Hou, SX.(2026).Inhibition of the cancer stem cell immune checkpoint SOAT1 suppresses regulatory T cell functions through a trans-cellular 20(S)-Hydroxycholesterol-GPR132 pathway in mice.Nat. Commun.,17(1).
MLA	Ding, YH,et al."Inhibition of the cancer stem cell immune checkpoint SOAT1 suppresses regulatory T cell functions through a trans-cellular 20(S)-Hydroxycholesterol-GPR132 pathway in mice".Nat. Commun. 17.1(2026).

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