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GARP 作为癌症和自身免疫中调节性 T 细胞调节的治疗靶点。

GARP as a Therapeutic Target for the Modulation of Regulatory T Cells in Cancer and Autoimmunity.

机构信息

Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany.

Early Clinical Development Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.

出版信息

Front Immunol. 2022 Jul 8;13:928450. doi: 10.3389/fimmu.2022.928450. eCollection 2022.

Abstract

Regulatory T cells (Treg) play a critical role in immune homeostasis by suppressing several aspects of the immune response. Herein, Glycoprotein A repetitions predominant (GARP), the docking receptor for latent transforming growth factor (LTGF-β), which promotes its activation, plays a crucial role in maintaining Treg mediated immune tolerance. After activation, Treg uniquely express GARP on their surfaces. Due to its location and function, GARP may represent an important target for immunotherapeutic approaches, including the inhibition of Treg suppression in cancer or the enhancement of suppression in autoimmunity. In the present review, we will clarify the cellular and molecular regulation of GARP expression not only in human Treg but also in other cells present in the tumor microenvironment. We will also examine the overall roles of GARP in the regulation of the immune system. Furthermore, we will explore potential applications of GARP as a predictive and therapeutic biomarker as well as the targeting of GARP itself in immunotherapeutic approaches.

摘要

调节性 T 细胞(Treg)通过抑制免疫反应的几个方面在免疫稳态中发挥关键作用。在此,糖蛋白 A 重复为主(GARP)作为潜伏转化生长因子(LTGF-β)的对接受体,促进其激活,在维持 Treg 介导的免疫耐受中发挥关键作用。激活后,Treg 细胞在其表面独特地表达 GARP。由于其位置和功能,GARP 可能代表免疫治疗方法的一个重要靶点,包括抑制癌症中的 Treg 抑制或增强自身免疫中的抑制。在本综述中,我们将阐明 GARP 表达的细胞和分子调节,不仅在人类 Treg 中,而且在肿瘤微环境中存在的其他细胞中。我们还将研究 GARP 在免疫系统调节中的整体作用。此外,我们将探讨 GARP 作为预测和治疗生物标志物的潜在应用,以及 GARP 本身在免疫治疗方法中的靶向作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4522/9309211/3a962ea49ae5/fimmu-13-928450-g001.jpg

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