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维斯塔缺乏在乳腺癌中通过调节巨细胞两极分化产生抗瘤作用

Shasha Jin¹, Wanmei Liu¹, Xiaoyu He¹

¹New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China.

International immunopharmacology

|May 31, 2024

概括

在乳腺癌中,V-域免疫球蛋白抑制T细胞激活 (VISTA) 调节了巨细胞两极分化. 抑制VISTA促进抗瘤M1巨细胞,并通过调节STAT信号来减少瘤生长.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
细胞生物学细胞生物学

背景情况:

与瘤相关的巨细胞 (TAMs) 经常表现出一种亲瘤的M2表型,这对乳腺癌的发展至关重要.
维域免疫球蛋白抑制T细胞激活 (VISTA) 是一种新兴的免疫治疗点,但其在巨细胞调节中的作用尚未被探索.

研究的目的:

在乳腺癌的背景下调查VISTA在调节巨分化中的功能.
阐明VISTA影响巨细胞行为和乳腺癌进展的分子机制.

主要方法:

单细胞RNA测序 (scRNA-seq) 用于识别巨细胞子集群中的VISTA表达.
在体外测试以评估在VISTA调节后的巨细胞极化 (M1/M2),增殖和细胞化.
使用VISTA缺乏的小鼠进行体内研究,以评估瘤生长动态.

主要成果:

在乳腺癌中,VISTA在多个巨细胞群中表达很高.
缺少VISTA促进了M1极化,抑制了M2极化,并减少了M2条件下的中等诱导的4T1细胞增殖和细胞化.
在小鼠中,VISTA缺乏导致瘤生长的减少,与M1巨细胞的增加和M2巨细胞的减少有关.
维斯塔通过STAT1和STAT6信号通路调节巨细胞极化.

结论:

这项研究是首次证明VISTA在调节乳腺癌中巨细胞极化中的关键作用.
维斯塔通过通过STAT信号通路调节巨细胞极化,影响乳腺癌的进展,呈现出潜在的治疗标.

关键词:

乳腺癌乳腺癌乳腺癌免疫治疗是一种免疫疗法.巨细胞是一个巨细胞.两极化的偏化在视野中看到的.

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