在固体瘤中,desmoplastic stroma限制T细胞扩散,并调解免疫排除和免疫抑制
Zebin Xiao1, Leslie Todd1, Li Huang1
1Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Nature communications
|August 22, 2023
概括
用FAP向的CAR T细胞向与癌症相关的纤维细胞 (CAF) 会重塑瘤微环境. 这种方法增加了对后续免疫疗法的敏感性,如向美索林的CAR T细胞和抗PD-1疗法.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 癌症生物学 癌症生物学
背景情况:
- 固体瘤中的质性瘤对基于T细胞的免疫疗法构成重大障碍.
- 精确的机制,通过这种树皮屏障阻碍治疗仍然不完全理解.
研究的目的:
- 研究癌症相关纤维细胞 (CAFs) 在调解免疫治疗耐药性的作用.
- 探索针对CAFs的纤维细胞激活蛋白 (FAP) 的治疗潜力.
主要方法:
- 使用针对FAP的仿真抗原受体 (CAR) T细胞治疗已确立的松性胰腺瘤.
- 评估FAP+CAF枯竭对瘤结构和免疫细胞透的影响.
- 评估后续治疗的疗效与中素向的CAR-T细胞和抗PD-1抗体疗法.
主要成果:
- FAP+ CAFs的耗尽破坏了脱质基质,增加了瘤对免疫治疗的敏感性.
- 向FAP+CAF克服了依赖性T细胞排斥和抑制.
- 这一策略促进了内源性CD8+T细胞和NK细胞的透,同时减少了髓状细胞的积累.
结论:
- 通过FAP+CAFs向脱质层是一种可行的策略,可以提高免疫治疗的疗效.
- 结合侧膜向和瘤细胞向疗法,为治疗耐药癌症提供了一个有前途的方法.
- 这些发现支持临床试验,将FAP向疗法与其他免疫疗法结合起来.
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