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CCL22 在肿瘤微环境中的信号传导作用。

CCL22 Signaling in the Tumor Environment.

机构信息

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.

Institute of Pathology of the Ludwig-Maximilians-Universität München, Munich, Germany.

出版信息

Adv Exp Med Biol. 2020;1231:79-96. doi: 10.1007/978-3-030-36667-4_8.

Abstract

T cell-mediated elimination of malignant cells is one cornerstone of endogenous and therapeutically induced antitumor immunity. Tumors exploit numerous regulatory mechanisms to suppress T cell immunity. Regulatory T cells (T regs) play a crucial role in this process due to their ability to inhibit antitumoral immune responses and they are known to accumulate in various cancer entities. The chemokine CCL22, predominately produced by dendritic cells (DCs), regulates T reg migration via binding to its receptor CCR4. CCL22 controls T cell immunity, both by recruiting T regs to the tumor tissue and by promoting the formation of DC-T reg contacts in the lymph node. Here, we review the current knowledge on the role of CCL22 in cancer immunity. After revising the principal mechanisms of CCL22-induced immune suppression, we address the factors leading to CCL22 expression and ways of targeting this chemokine therapeutically. Therapeutic interventions to the CCL22-CCR4 axis may represent a promising strategy in cancer immunotherapy.

摘要

T 细胞介导的恶性细胞消除是内源性和治疗性诱导抗肿瘤免疫的基石之一。肿瘤利用多种调节机制来抑制 T 细胞免疫。调节性 T 细胞(Tregs)由于其抑制抗肿瘤免疫反应的能力而在这一过程中发挥着关键作用,并且已知它们在各种癌症实体中积累。趋化因子 CCL22 主要由树突状细胞(DCs)产生,通过与其受体 CCR4 结合来调节 Treg 的迁移。CCL22 通过将 Treg 招募到肿瘤组织中,并促进淋巴结中 DC-Treg 接触的形成,来控制 T 细胞免疫。在这里,我们综述了 CCL22 在癌症免疫中的作用的最新知识。在修正了 CCL22 诱导免疫抑制的主要机制之后,我们研究了导致 CCL22 表达的因素以及靶向这种趋化因子的治疗方法。针对 CCL22-CCR4 轴的治疗干预可能是癌症免疫治疗的一种有前途的策略。

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