嵌合抗原受体（CAR）-T细胞最近已成为治疗化疗难治性或复发性血癌患者的有效治疗方法，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。骨髓瘤。然而，大多数患者都会出现对 CAR-T 细胞疗法的耐药性。在这篇综述中，我们通过分析CAR-T细胞功能障碍、肿瘤内在耐药性和免疫抑制性肿瘤微环境，总结了CAR-T细胞免疫治疗的耐药机制。我们讨论了当前克服多种耐药机制的研究策略，包括优化 CAR 设计、改善体内 T 细胞功能和持久性、调节免疫抑制肿瘤微环境以及协同组合策略。© 2023。Springer Nature Limited。

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.© 2023. Springer Nature Limited.