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骨髓瘤细胞内在的ANXA1升高和T细胞功能障碍有助于在CAR-T治疗后的BCMA阴性复发
Shuangshuang Yang1, Guixiang Wang2, Jiahuan Chen2
1State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
概括
抗BCMA CAR-T治疗后多发性髓瘤 (MM) 复发与表达高ANXA1.1的BCMA阴性细胞有关. 向ANXA1可能会克服耐药性,并改善MM患者的CAR-T疗效.
科学领域:
- 血液学 血液学 血液学
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 在抗B细胞成熟抗原 (BCMA) 仿真抗原受体工程T (CAR-T) 细胞治疗后,多发性髓瘤 (MM) 的复发发生了尽管最初的反应.
- 在CAR-T治疗后导致MM复发的因素仍然不完全理解.
研究的目的:
- 在接受抗BCMA CAR-T细胞治疗的患者中研究MM复发的机制.
- 确定潜在的治疗点,以克服BCMA阴性MM的耐药性.
主要方法:
- 来自复发MM患者的骨髓样本的单细胞转录组测序.
- 试验室试验评估了Annexin A1 (ANXA1) 在MM细胞增殖和CAR-T细胞功能中的作用.
- 在 vivo 中评估ANXA1抑制的疗效的小鼠模型.
主要成果:
- 在CAR-T治疗后复发的MM细胞缺乏BCMA表达,但保留了瘤克隆性.
- BCMA阴性MM细胞表现出高ANXA1表达,与预后不佳相关.
- ANXA1通过AMPKα信号传递和受损的CAR-T细胞活性促进了BCMA阴性MM细胞的生长.
- 在体内,ANXA1阻断降低了BCMA阴性MM增殖和瘤负担.
结论:
- ANXA1是BCMA阴性MM增长和CAR-T耐药性的关键驱动因素.
- 准ANXA1代表了清除BCMA负MM的有希望的策略.
- 抑制ANXA1可以提高在MM中CAR-T细胞治疗的有效性.
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