骨髓衍生中细胞阻碍AML向的CD8+克隆效应体和CAR T细胞功能,同时促进与衰老相关的表型
Russell Towers1,2, Lidia Trombello1,3,4, Maximilian Fusenig1,5
1Medical Clinic 1 (MK1), University Hospital Carl Gustav Carus, TU Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
Cancer immunology, immunotherapy : CII
|January 17, 2024
概括
介酶体 stromal 细胞 (MSCs) 可以通过抑制 T 细胞扩张和功能来阻碍急性髓性白血病 (AML) 的免疫治疗. 准MSC可能会改善针对AML的组合疗法.
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:
- 介酶体 stromal 细胞 (MSCs) 是已知的免疫调节器.
- 它们对针对急性髓性白血病 (AML) 的基于T细胞的免疫疗法的影响需要进一步调查.
研究的目的:
- 为了确定MSC是否阻碍抗白血病T细胞活性.
- 在AML免疫疗法中研究MSC诱导的T细胞衰老.
主要方法:
- 与白血病特异性细胞毒性T淋巴细胞 (CTLs) 和仿真抗原受体 (CAR) T细胞一起培养MSCs.
- 对T细胞细胞毒性,细胞因子分泌,扩张和衰老标记物的评估 (CD28-,CD57+).
主要成果:
- MSCs通过印胺2,3-二氧化酶1 (IDO-1) 活性抑制了CAR T细胞扩张.
- MSCs减少了从CTL和CAR T细胞释放的干扰素 (IFNγ) 和互白素-2 (IL-2).
- MSCs诱导了一种衰老的T细胞表型 (CD28loCD27loCD57+KLRG1+).
结论:
- MSCs是抗白血病T细胞的强有力的抑制剂.
- 针对MSC的机制可以提高AML免疫疗法的疗效.
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