CAR-T细胞疗法重塑了内源性T细胞景观,并预测了多发性骨髓瘤的治疗反应。

IF 13.4 1区 医学 Q1 HEMATOLOGY
Julia Frede,Julia C Poller,Kayleen Shi,Hannah Stuart,Noori Sotudeh,Claire Havig,Klothilda Lim,Caroline R M Wiggers,Eugene Y Cho,Tushara Vijaykumar,Jianlin Liu,Johannes M Waldschmidt,Monica S Nair,Praveen Anand,Valeriya Dimitrova,Anna Montanaro,Andrew J Yee,Nikhil C Munshi,Kenneth C Anderson,Nathan Martin,Shari M Kaiser,Marc-Steffen Raab,Noopur S Raje,Birgit Knoechel,Jens G Lohr
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引用次数: 0

摘要

虽然大多数患者最初对CAR-T细胞治疗有反应,但反应往往不是持久的,随后的免疫疗法显示出越来越少的成功。在这项研究中,我们研究了在单细胞分辨率下接受抗bcma CAR-T细胞治疗的骨髓瘤患者中CAR-T细胞与免疫微环境之间的共同进化动力学。我们的研究结果强调了CAR-T细胞治疗对内源性T细胞景观的变革性影响。我们确定了一种新的过渡性CD8 + T细胞群,它可以预测不良的治疗结果。这一群体的出现与内源性T细胞库的耗尽和功能性T细胞亚群的组成进化相吻合。CAR-T细胞疗法诱导的内源性T细胞区室的这些变化可能导致免疫能力不足和肿瘤控制。我们的研究结果强调了靶向TIM3/GAL9相互作用以减轻T细胞衰竭、凋亡和缺乏持久性的潜力,为优化基于T细胞的癌症免疫疗法提供了有希望的途径。我们提供了一个框架来评估和操纵免疫系统的“里程”,作为预测标记和治疗机会,以防止重复的免疫治疗变得越来越不成功,即使是针对不同的抗原。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The endogenous T cell landscape is reshaped by CAR-T cell therapy and predicts treatment response in multiple myeloma.
While most patients initially respond to CAR-T cell treatment, responses often are not durable and subsequent lines of immunotherapy show diminishing success. In this study, we investigated the co-evolutionary dynamics between CAR-T cells and the immune microenvironment in myeloma patients undergoing anti-BCMA CAR-T cell therapy at single-cell resolution. Our findings highlight the transformative impact of CAR-T cell treatment on the endogenous T cell landscape. We identify a novel transitional CD8 + T cell population that is predictive of poor treatment outcomes. The emergence of this population coincides with the depletion of the endogenous T cell repertoire and compositional evolution of functional T cell subsets. These changes in the endogenous T cell compartment induced by CAR-T cell therapy may contribute to inadequate immune capacity and tumor control. Our findings highlight the potential of targeting TIM3/GAL9 interactions to mitigate T cell exhaustion, apoptosis and lack of persistence, offering promising avenues for optimizing T cell-based cancer immunotherapies. We provide a framework for assessing and manipulating the 'mileage' of the immune system as predictive marker and therapeutic opportunity to prevent repeated immunotherapies from becoming increasingly less successful, even when targeting distinct antigens.
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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
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