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Tertiary Lymphoid Structures and B cells: Clinical impact and therapeutic modulation in cancer
Seminars in Immunology ( IF 7.4 ) Pub Date : 2020-11-25 , DOI: 10.1016/j.smim.2020.101406
Catherine Sautès-Fridman, Johanna Verneau, Cheng-Ming Sun, Marco Moreira, Tom Wei-Wu Chen, Maxime Meylan, Florent Petitprez, Wolf Herman Fridman

Tumors progression is under the control of a heterogeneous microenvironment composed of immune cells, fibroblasts, blood and lymphatic vessels, in which T cells have been demonstrated to be major actors, through their cytotoxic and cytokine producing effector functions and their long term memory that protects against metastasis. In this scenario, lessons from mouse models taught that B cells exert a protumoral role, via macrophage-dependent activation of inflammation. However, it became progressively evident from studies in patients with human cancers that the anti-tumor responses can be generated and controlled in tertiary lymphoid structures (TLS) that concentrate most of the intratumoral B cells and where B cells can differentiate into plasma cells and memory cells. Furthermore, recent studies demonstrated that the presence in tumors of B cells and TLS are associated with favorable outcome in patients treated by immunotherapy, unraveling TLS as a new predictive marker of anti-tumor response human cancers. This review encompasses the characteristics and functions of TLS and of B cells in human tumors, their prognostic and theranostic impact and summarizes the mouse models used to induce TLS neogenesis in tumors.



中文翻译:

三级淋巴结构和 B 细胞:癌症的临床影响和治疗调节

肿瘤进展受由免疫细胞、成纤维细胞、血液和淋巴管组成的异质微环境的控制,其中 T 细胞已被证明是主要参与者,通过它们的细胞毒性和细胞因子产生效应功能以及它们的长期记忆来防止转移。在这种情况下,小鼠模型的经验教训表明,B 细胞通过巨噬细胞依赖性炎症激活发挥促肿瘤作用。然而,从人类癌症患者的研究中逐渐明显看出,可以在三级淋巴结构 (TLS) 中产生和控制抗肿瘤反应,该结构集中了大部分肿瘤内 B 细胞,并且 B 细胞可以分化为浆细胞和记忆细胞。此外,最近的研究表明,肿瘤中 B 细胞和 TLS 的存在与接受免疫疗法治疗的患者的良好结果相关,揭示了 TLS 作为人类癌症抗肿瘤反应的新预测标志物。本综述涵盖了人类肿瘤中 TLS 和 B 细胞的特征和功能、它们的预后和治疗诊断影响,并总结了用于诱导肿瘤中 TLS 新生的小鼠模型。

更新日期:2020-12-09
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