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Abstract: chimeric antigen receptor-T (CAR-T) cell therapy, as a novel cellular immunotherapy, has dramatically reshaped the landscape of cancer treatment, especially in hematological malignancies. However, relapse is still one of the most troublesome obstacles to achieving broad clinical application. The intrinsic factors and superior adaptability of tumor cells mark a fundamental aspect of relapse. The unique biological function of CAR-T cells governed by their special CAR construction also affects treatment efficacy. Moreover, complex cross-interactions among CAR-T cells, tumor cells, and the tumor microenvironment (TME) profoundly influence clinical outcomes concerning CAR-T cell function and persistence. Therefore, in this review, based on the most recent discoveries, we focus on the challenges of relapse after CAR-T cell therapy in b-cell malignancies from the perspective of tumor cells, CAR-T cells, and the TME. We also discuss the corresponding basic and clinical approaches that may overcome the problem in the future. We aim to provide a comprehensive understanding for scientists and physicians that will help improve research and clinical practice.

B细胞恶性肿瘤经CAR-T细胞治疗后复发：挑战与未来

顾天宁^1,2,3,4，朱萌^1,2,3,4，黄河^1,2,3,4，胡永仙^1,2,3,4
1浙江大学医学院附属第一医院骨髓移植中心，中国杭州市，310003
²浙江大学医学中心良渚实验室，中国杭州市，311121
³浙江大学血液学研究所，中国杭州市，310058
⁴干细胞与细胞免疫治疗浙江省工程研究中心，中国杭州市，310058
概要：嵌合抗原受体T(CAR-T)细胞疗法作为一种新型的细胞免疫疗法，极大地改变了癌症治疗的格局，尤其是在血液系统恶性肿瘤中。然而，CAR-T细胞治疗后复发仍然是影响其广泛应用于临床的主要障碍之一。肿瘤细胞内在特性和较强的适应能力，是复发的一个重要原因。由于特殊CAR结构的存在，CAR-T细胞具有的独特生物学功能同样影响治疗效果。此外，肿瘤微环境中错综复杂的相互作用深刻影响CAR-T细胞功能及临床预后。因此，本综述基于最新发现，从肿瘤细胞、CAR-T细胞和肿瘤微环境角度，关注B细胞恶性肿瘤经CAR-T细胞治疗后复发，讨论未来相应的基础和临床策略，以提供全面的认识，有助于提高研究和临床应用。

关键词：嵌合抗原受体T（CAR-T）；B细胞恶性肿瘤；复发机制；策略

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