肿瘤细胞治疗研究
英文原题：Mechanisms of resistance to chimeric antigen receptor-T cells in haematological malignancies.
嵌合抗原受体（CAR）-T细胞近来已成为治疗化疗难治性或复发性血液系统恶性肿瘤患者的强大治疗方法，包括急性淋巴细胞白血病、弥漫性大B细胞淋巴瘤、滤泡性淋巴瘤、套细胞淋巴瘤和多发性骨髓瘤。
嵌合抗原受体（CAR）T细胞近来成为治疗化疗难治或复发血液系统恶性肿瘤的有力手段，适用疾病包括急性淋巴细胞白血病、弥漫大B细胞淋巴瘤、滤泡性淋巴瘤、套细胞淋巴瘤及多发性骨髓瘤。然而，多数患者仍会对CAR-T细胞疗法产生耐药。本综述通过分析CAR-T细胞功能障碍、肿瘤内在耐药性及免疫抑制性肿瘤微环境，总结CAR-T免疫治疗的耐药机制，并讨论克服多种耐药机制的当前研究策略，包括优化CAR设计、改善体内T细胞功能和持久性、调节免疫抑制性肿瘤微环境以及采用协同联合治疗策略。
Chimeric antigen receptor (CAR)-T cells have recently emerged as a powerful therapeutic approach for the treatment of patients with chemotherapy-refractory or relapsed blood cancers, including acute lymphoblastic leukaemia, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma and multiple myeloma. Nevertheless, resistance to CAR-T cell therapies occurs in most patients. In this Review, we summarize the resistance mechanisms to CAR-T cell immunotherapy by analysing CAR-T cell dysfunction, intrinsic tumour resistance and the immunosuppressive tumour microenvironment. We discuss current research strategies to overcome multiple resistance mechanisms, including optimization of the CAR design, improvement of in vivo T cell function and persistence, modulation of the immunosuppressive tumour microenvironment and synergistic combination strategies.
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