在抗CD19CAR T细胞治疗后获得免疫抑制微环境与T细胞功能障碍和抗药性有关
Marianna Ponzo1,2, Lorenzo Drufuca3,4, Chiara Buracchi5
1Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
Journal for immunotherapy of cancer
|October 24, 2025
概括
针对B细胞急性淋巴细胞白血病 (B-ALL) 的CAR T细胞治疗可能会受到瘤微环境变化的阻碍. 骨髓细胞激活和免疫失调途径可能会限制治疗的有效性.
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:
- 针对CD19的化学抗原受体 (CAR) T细胞对B细胞急性淋巴细胞白血病 (B-ALL) 有效.
- 瘤微环境在CAR T细胞治疗反应中的作用尚未完全理解.
研究的目的:
- 研究CAR T细胞治疗对B-ALL.骨髓免疫微环境的影响.
- 识别导致治疗耐药性的机制.
主要方法:
- 单细胞RNA测序和骨髓免疫细胞的光谱流细胞计从B-ALL患者在CAR T细胞治疗前后.
- 分析免疫细胞的变化,信号通路和细胞间通信.
主要成果:
- 用CAR T细胞治疗诱导了显著的微环境变化,包括骨髓细胞扩张,干扰素反应,缺氧和TGF-β信号传递.
- 观察到骨髓衍生抑制细胞 (MDSC) 的增加和CD8+ T细胞的耗尽.
- 在内源性T细胞上的PD-1表达与缺乏持久反应相关.
- HIF-1α,VEGF和TGFBR2被确定为T细胞功能障碍的关键调解者.
- 在小鼠模型中注入CAR T细胞导致MDSC积累,缺氧和T细胞耗尽.
结论:
- 卡尔T细胞疗法触发了髓状细胞激活,导致免疫失调路径.
- 这些途径可能会抵消B-ALL中CAR-T细胞的治疗作用.
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