嵌合受体抗原T细胞（CAR-T细胞）疗法已经在血液恶性肿瘤的免疫治疗中证明其有效性和治疗潜力，代表了癌症治疗领域的一个有希望的突破。尽管CAR-T细胞疗法在B细胞淋巴瘤中显示出了疗效，但应答变异性、耐药性和副作用仍然是持续存在的挑战。肿瘤微环境（TME）在B细胞淋巴瘤的CAR-T细胞疗法中起着复杂的作用。TME是一个复杂而动态的环境，包括各种细胞类型、细胞因子和细胞外基质组分，所有这些都可以影响CAR-T细胞的功能和行为。本综述讨论了CAR-T细胞的设计原则、B细胞淋巴瘤中的TME以及TME如何影响CAR-T细胞功能的机制。我们讨论了调节TME、靶向免疫抑制细胞、克服抑制性信号传导、提高CAR-T细胞浸润和持久性的新兴策略。因此，这些过程增强了CAR-T细胞疗法在B细胞淋巴瘤中的疗效，改善了患者预后。进一步的研究还需要探究输注后发生的分子和细胞事件，包括TME组成的变化、免疫细胞相互作用、细胞因子信号传导和潜在的耐药机制。了解这些过程将有助于开发更有效的CAR-T细胞疗法和减轻治疗相关毒性的策略。© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.

Chimeric receptor antigen T cell (CAR-T cell) therapy has demonstrated effectiveness and therapeutic potential in the immunotherapy of hematological malignancies, representing a promising breakthrough in cancer treatment. Despite the efficacy of CAR-T cell therapy in B-cell lymphoma, response variability, resistance, and side effects remain persistent challenges. The tumor microenvironment (TME) plays an intricate role in CAR-T cell therapy of B-cell lymphoma. The TME is a complex and dynamic environment that includes various cell types, cytokines, and extracellular matrix components, all of which can influence CAR-T cell function and behavior. This review discusses the design principles of CAR-T cells, TME in B-cell lymphoma, and the mechanisms by which TME influences CAR-T cell function. We discuss emerging strategies aimed at modulating the TME, targeting immunosuppressive cells, overcoming inhibitory signaling, and improving CAR-T cell infiltration and persistence. Therefore, these processes enhance the efficacy of CAR-T cell therapy and improve patient outcomes in B-cell lymphoma. Further research will be needed to investigate the molecular and cellular events that occur post-infusion, including changes in TME composition, immune cell interactions, cytokine signaling, and potential resistance mechanisms. Understanding these processes will contribute to the development of more effective CAR-T cell therapies and strategies to mitigate treatment-related toxicities.© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.