在T调节细胞和与癌症相关的纤维细胞之间形成免疫突触促进了瘤的发展
Athina Varveri1,2, Miranta Papadopoulou1,2, Zacharias Papadovasilakis2,3
1Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation Academy of Athens, Athens, Greece.
Nature communications
|June 11, 2024
概括
与癌症相关的纤维细胞 (CAFs) 与调节性T细胞 (Tregs) 形成突触,以抑制抗瘤免疫力. 这种依赖于自的相互作用涉及CAF处理抗原并促进Treg耐受性,阻碍抗癌反应.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 细胞生物学 细胞生物学
背景情况:
- 癌症相关纤维细胞 (CAF) 是瘤微环境的关键组成部分,影响瘤的进展.
- 通过CAF调节抗瘤免疫力的精确机制尚未完全理解.
研究的目的:
- 为了研究α-平滑肌肉actin-positive (α-SMA+) CAFs在调节抗瘤免疫力的作用.
- 阐明CAF介导免疫抑制的细胞和分子机制.
主要方法:
- 利用多种瘤模型和患者瘤活检.
- 采用了包括免疫光在内的技术用于突触可视化,抗原处理试验和单细胞转录组学.
- 在α-SMA+ CAF中生成了与自相关的基因5 (Atg5) 的条件淘汰模型.
主要成果:
- 在瘤中,α-SMA+ CAF与Foxp3+调节性T细胞 (Tregs) 形成免疫突触.
- CAFs细胞化和处理瘤抗原,诱导抗原特异性Treg激活,增殖和运动停止.
- CAFs表现出类似自细胞的结构,自细胞和抗原呈现途径富含α-SMA表达集群.
- 在CAF中Atg5的有条件淘汰导致炎症重编程,减少Treg透,并减弱瘤发育.
结论:
- α-SMA+ CAFs采用一种依赖自的机制,通过与Tregs进行接触来抑制抗瘤免疫力.
- 这种相互作用涉及CAFs对Tregs的抗原呈现,促进了宽容性免疫环境.
- 向CAF-Treg相互作用或自可能是增强抗瘤免疫力的新疗法策略.
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