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肿瘤引流淋巴结免疫抑制微环境形成机制及靶向治疗研究进展
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Abstract:
肿瘤引流淋巴结(TDLN)是抗肿瘤免疫调控的核心部位。TDLN不仅是诱导肿瘤免疫应答的关键场所，更是介导免疫检查点抑制剂响应的重要部位。当前，领域内的研究多聚焦于肿瘤局部免疫抑制微环境的形成机制及其导致免疫治疗耐药的机制及干预策略，而针对TDLN免疫抑制调控网络的系统性探索较为薄弱。然而，越来越多的研究表明，在肿瘤驯化下TDLN内免疫抑制微环境的形成是肿瘤逃逸免疫监视的关键环节：如调节性T细胞、调节性B细胞、调节性树突状细胞等免疫抑制细胞在此构建免疫抑制微环境，直接影响T细胞活化及分化路径，进而驱动肿瘤免疫逃逸，最终显著削弱免疫检查点抑制剂疗效。本文聚焦TDLN这一被忽视的免疫调控关键环节，以其免疫抑制微环境的形成机制为重点，并总结基于TDLN为靶点的治疗策略，为深入理解肿瘤免疫检查点抑制剂疗法的耐药机制、开发新型免疫检查点抑制剂联合治疗策略提供理论依据。
Tumor-draining lymph nodes (TDLNs) serve as a central hub for regulating anti-tumor immunity. They are not only key loci for inducing tumor immune responses but also critical sites mediating the efficacy of immune checkpoint inhibitors (ICIs). Currently, most research in the field focuses on the formation mechanisms of the local immunosuppressive tumor microenvironment, as well as the mechanisms underlying immunotherapy resistance and corresponding intervention strategies. However, systematic exploration of the immunosuppressive regulatory network within TDLNs remains insufficient. Nevertheless, a growing body of evidence indicates that the formation of an immunosuppressive microenvironment in TDLNs under tumor conditioning is a pivotal step for tumors to escape immune surveillance. For instance, immunosuppressive cells such as regulatory T cells (Tregs), regulatory B cells (Bregs), and regulatory dendritic cells (DCregs) accumulate here to establish an immunosuppressive microenvironment. This directly impairs T cell activation and differentiation pathways, thereby driving tumor immune evasion and ultimately significantly compromising the therapeutic efficacy of ICIs. Focusing on TDLNs—this overlooked key node in immune regulation—this review emphasizes the formation mechanisms of their immunosuppressive microenvironment and summarizes TDLN-targeted therapeutic strategies. It aims to provide a theoretical basis for a deeper understanding of the resistance mechanisms to tumor ICI therapy and the development of novel combination therapeutic strategies involving ICIs.
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