CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Mechanisms of Resistance to Chimeric Antigen Receptor T Cell Therapy.
Mechanisms of Resistance to Chimeric Antigen Receptor T Cell Therapy.
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CAR-T 细胞治疗显著改变了难治性血液系统恶性肿瘤的治疗格局，包括大 B 细胞淋巴瘤、多发性骨髓瘤和白血病。尽管既往预后极差患者的缓解率有所提高，但要使 CAR-T 疗法达到可靠、持久的疗效，仍存在若干障碍。本文综述了有关肿瘤对 CAR-T 耐药机制的研究证据，包括靶抗原丢失的影响、T 细胞耗竭导致效应功能衰退、持久缓解所需的 CAR-T 最大扩增程度、炎症环境和免疫抑制性肿瘤微环境带来的负面影响，以及与最佳治疗结局相关的肿瘤与效应细胞比例。未来 CAR-T 疗法应致力于减轻这些弱点，以增强这一突破性治疗的疗效。
CAR T cell therapy has significantly shaped the treatment landscape for refractory hematologic malignancies including large B-cell lymphomas, multiple myeloma, and leukemias. While response rates for a previously dismal prognosis have improved, certain obstacles still remain to achieving CAR T infallibility.
In this article, we review the data surrounding proposed resistance mechanisms of tumors to CAR T, including the implications of target loss, exhausted T cells as effete effectors, the necessity of maximal CAR T expansion to durable response, the negative impact of an inflammatory milieu and a suppressive tumor microenvironment, and the optimal tumor-to-effector ratio that associates with best outcomes. The future of CAR T should aim to mitigate these weaknesses in order to bolster the efficacy of this revolutionary therapy.
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