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揭示癌症的沉默破坏者:调节性T细胞作为免疫疗法的治疗靶点。

Unmasking cancer's silent saboteurs: T regulatory cells as therapeutic targets in immunotherapy.

作者信息

Khudeir Joudi Feras, Elkord Eyad

机构信息

Department of Applied Biology, College of Science, University of Sharjah, Sharjah, United Arab Emirates.

Human Genetics and Stem Cell Laboratory, Research Institute of Sciences and Engineering, University of Sharjah, Sharjah, United Arab Emirates.

出版信息

Expert Rev Clin Immunol. 2025 Nov;21(11):1583-1600. doi: 10.1080/1744666X.2025.2585521. Epub 2025 Nov 9.

DOI:10.1080/1744666X.2025.2585521
PMID:41199577
Abstract

INTRODUCTION

T regulatory cells (Tregs) are key modulators of the immune system with dual roles. While protective against autoimmunity, Tregs can exhibit immunosuppressive capabilities, allowing the tumor to evade immune recognition and destruction, and favoring tumor progression. Targeting Tregs to reduce their immunosuppressive ability offers a promising strategy to boost anti-tumor immunity and improve cancer treatment outcomes.

AREAS COVERED

This review explores the role of Tregs in the immune system, delves into their contribution to cancer and tumor progression, and highlights therapeutic strategies targeting Tregs, along with innovative delivery systems.

EXPERT OPINION

Targeting tumor-infiltrating regulatory T cells (Tregs) represents a promising but complex approach in cancer immunotherapy. However, its success is limited by the risk of autoimmunity, inefficient intratumoral delivery, and patient immune heterogeneity. Precision strategies integrating biomarker-guided stratification, single-cell, and spatial profiling can improve selectivity and therapeutic outcomes. Identifying tumor-specific Treg markers and distinguishing stable, suppressive Tregs from more plastic or 'fragile' subsets are essential for advancing targeted immunotherapies. Partial functional reprogramming of tumor-resident Tregs, rather than their complete depletion, offers a strategy to weaken their suppressive capacity while retaining peripheral immune regulation, thus promoting local anti-tumor responses without disrupting tolerance.

摘要

引言

调节性T细胞(Tregs)是免疫系统的关键调节因子,具有双重作用。Tregs在预防自身免疫方面具有保护作用,但也可表现出免疫抑制能力,使肿瘤能够逃避免疫识别和破坏,从而促进肿瘤进展。靶向Tregs以降低其免疫抑制能力为增强抗肿瘤免疫力和改善癌症治疗效果提供了一种有前景的策略。

涵盖领域

本综述探讨了Tregs在免疫系统中的作用,深入研究了它们对癌症和肿瘤进展的贡献,并重点介绍了靶向Tregs的治疗策略以及创新的递送系统。

专家观点

靶向肿瘤浸润调节性T细胞(Tregs)在癌症免疫治疗中是一种有前景但复杂的方法。然而,其成功受到自身免疫风险、肿瘤内递送效率低下以及患者免疫异质性的限制。整合生物标志物引导分层、单细胞和空间分析的精准策略可以提高选择性和治疗效果。识别肿瘤特异性Treg标志物以及区分稳定的、具有抑制作用的Tregs与更具可塑性或“脆弱”的亚群对于推进靶向免疫治疗至关重要。对肿瘤驻留Tregs进行部分功能重编程,而不是完全耗竭它们,提供了一种在保留外周免疫调节的同时削弱其抑制能力的策略,从而在不破坏耐受性的情况下促进局部抗肿瘤反应。

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