Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies.
Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies.
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DOI：
10.1136/jitc-2021-002591
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发表时间：
2021-07
影响因子：
10.9
通讯作者：
Koyama S
中科院分区：
文献类型：
--
作者：
Nishikawa H;Koyama S
随着癌症免疫疗法（如免疫检查点抑制剂）在多种癌症类型中的广泛应用，肿瘤微环境（TME）中的免疫景观对于确定最佳癌症治疗变得非常重要。肿瘤可以在免疫学上分为两类：基于免疫细胞浸润的程度和它们的活化状态的发炎和非发炎。一般来说，免疫疗法对于发炎的肿瘤比对于非发炎的肿瘤更优选。调节性T细胞（Regulatory T cells，Tcells）是CD4+ T细胞的免疫抑制亚群，在维持自身免疫耐受和免疫稳态中发挥重要作用。在肿瘤免疫中，TdR损害健康个体中针对癌症的免疫监视，并损害荷瘤宿主中的抗肿瘤免疫应答。因此，TGFAP加速肿瘤细胞的免疫逃避，导致各种类型癌症的肿瘤发展和进展。因此，TcB被认为是癌症免疫治疗的关键治疗靶点。在许多类型的癌症中，在发炎和非发炎肿瘤中，在TME中观察到丰富的TME。不同肿瘤类型的TME中Treg积累、激活和存活的不同机制已经被揭示，这表明在选择最佳Treg靶向治疗时，理解每个患者中Treg浸润机制的重要性。在这里，我们回顾了最近的进展，了解机制导致Treg丰度在TME优化Treg靶向治疗。此外，除了靶向主要由Tregin表达的细胞表面分子的常规策略之外，靶向Tregin在每种肿瘤类型中特异性用于浸润、活化和存活的分子和信号传导途径的试剂被说明为新型Treg靶向疗法。免疫精准治疗的有效性取决于每个癌症患者TME的状况。
With the broad application of cancer immunotherapies such as immune checkpoint inhibitors in multiple cancer types, the immunological landscape in the tumor microenvironment (TME) has become enormously important for determining the optimal cancer treatment. Tumors can be immunologically divided into two categories: inflamed and non-inflamed based on the extent of immune cell infiltration and their activation status. In general, immunotherapies are preferable for the inflamed tumors than for non-inflamed tumors. Regulatory T cells (Tregs), an immunosuppressive subset of CD4+ T cells, play an essential role in maintaining self-tolerance and immunological homeostasis. In tumor immunity, Tregs compromise immune surveillance against cancer in healthy individuals and impair the antitumor immune response in tumor-bearing hosts. Tregs, therefore, accelerate immune evasion by tumor cells, leading to tumor development and progression in various types of cancer. Therefore, Tregs are considered to be a crucial therapeutic target for cancer immunotherapy. Abundant Tregs are observed in the TME in many types of cancer, both in inflamed and non-inflamed tumors. Diverse mechanisms of Treg accumulation, activation, and survival in the TME have been uncovered for different tumor types, indicating the importance of understanding the mechanism of Treg infiltration in each patient when selecting the optimal Treg-targeted therapy. Here, we review recent advances in the understanding of mechanisms leading to Treg abundance in the TME to optimize Treg-targeted therapy. Furthermore, in addition to the conventional strategies targeting cell surface molecules predominantly expressed by Tregs, reagents targeting molecules and signaling pathways specifically employed by Tregs for infiltration, activation, and survival in each tumor type are illustrated as novel Treg-targeted therapies. The effectiveness of immune precision therapy depends on conditions in the TME of each cancer patient.
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