CAR - T细胞介导的骨髓炎症导致血液毒性,有利于克隆造血

IF 14.6 1区 医学 Q1 CELL BIOLOGY
Myriam Ben Khelil, Ahmadreza Arbab, Janesa Srikanthan, Laura Marcos Kovandzic, Véronique Vergé, Arnaud Pagès, Jessica Rengassamy, Roula Amine-Hneineh, Marine Aglave, Rémy Jelin, Vincent Ribrag, Wassila Rahali, Paul-Auguste Goutebroze, Stéphane de Botton, Laurie Menger, Ileana Antony-Debré, Jean-Baptiste Micol, Christophe Marzac, Cristina Castilla Llorente, Camille Bigenwald
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引用次数: 0

摘要

尽管嵌合抗原受体(CAR) T细胞在治疗血液系统恶性肿瘤方面显示出优异的效果,但它们也会产生副作用。接受CAR - T细胞治疗的患者会经历持续的细胞减少或血液中毒。在这里,我们使用一个完全免疫的小鼠模型,总结了血液毒素,并证明了单独的淋巴消耗方案不足以诱导血液毒素,需要CAR - T细胞注射。对血液毒素患者骨髓(BM)样本的分析揭示了骨髓CAR - T细胞与血液毒素严重程度之间的相关性。CAR - T细胞表现出一种激活程序,导致强烈的炎症。此外,我们观察到在我们的患者队列中克隆造血率很高,并且在CAR - T细胞注射后的几个月内出现了不同的造血克隆。我们的研究为血液毒素的病理生理学提供了见解,并强调了长期随访研究的必要性,以确定这种强烈的BM炎症与克隆选择的相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CAR T cell–mediated bone marrow inflammation causes hematotoxicity and favors clonal hematopoiesis
Although chimeric antigen receptor (CAR) T cells have shown excellent results in treating hematological malignancies, they also cause side effects. Patients treated with CAR T cells experience persistent cytopenia or hematotox. Here, using a fully immunocompetent mouse model, we recapitulated hematotox and demonstrated that a lymphodepleting regimen alone was insufficient to induce hematotox and required CAR T cell injection. Analysis of bone marrow (BM) samples from patients experiencing hematotox revealed a correlation between BM CAR T cells and hematotox severity. CAR T cells exhibited an activated program, leading to intense inflammation. In addition, we observed a high rate of clonal hematopoiesis in our patient cohort and the emergence of distinct hematopoietic clones in the months after CAR T cell injection. Our study provides insights into the pathophysiology of hematotox and highlights the need for long-term follow-up studies to determine the relevance of this intense BM inflammation in clonal selection.
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
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