健康的免疫系统对于宿主抵抗外部病原体和维持体内平衡至关重要；然而，免疫抑制性肿瘤微环境（TME）会损害抗肿瘤免疫，促进肿瘤进展、侵袭和转移。近年来，许多研究发现Foxp3调节性T细胞（Treg）是主要的免疫抑制细胞，通过促进多种肿瘤相关细胞的发育和抑制效应免疫细胞的活性来促进TME的形成。考虑到 Tregs 在肿瘤进展中的作用，寻找新的治疗药物来靶向和消除肿瘤中的 Tregs 至关重要。尽管一些研究已经开发出靶向删除 Treg 的策略，以减少 TME 并支持肿瘤中效应 T 细胞的积累，但 Treg 靶向治疗系统性地影响 Treg 群体，并可能导致自身免疫性疾病的进展。然而，据了解，在疾病条件下，Foxp3 会经历几种明确的翻译后修饰 (PTM)，包括乙酰化、糖基化、磷酸化、泛素化和甲基化。这些 PTM 不仅提高或减弱 Foxp3 的转录活性，而且影响 Tregs 的稳定性和免疫抑制功能。各种研究表明，对参与 PTM 的酶进行药理学靶向可以显着影响 Foxp3 的 PTM；因此，它可能会影响癌症和/或自身免疫性疾病的进展。总体而言，本综述将有助于研究人员了解Tregs免疫抑制机制的进展、Foxp3的翻译后调控，以及针对TME中Tregs提高抗肿瘤免疫力的潜在治疗靶点和策略。版权所有© 2023 Riaz、黄和潘。

A healthy immune system is pivotal for the hosts to resist external pathogens and maintain homeostasis; however, the immunosuppressive tumor microenvironment (TME) damages the anti-tumor immunity and promotes tumor progression, invasion, and metastasis. Recently, many studies have found that Foxp3+ regulatory T (Treg) cells are the major immunosuppressive cells that facilitate the formation of TME by promoting the development of various tumor-associated cells and suppressing the activity of effector immune cells. Considering the role of Tregs in tumor progression, it is pivotal to identify new therapeutic drugs to target and deplete Tregs in tumors. Although several studies have developed strategies for targeted deletion of Treg to reduce the TME and support the accumulation of effector T cells in tumors, Treg-targeted therapy systematically affects the Treg population and may lead to the progression of autoimmune diseases. It has been understood that, nevertheless, in disease conditions, Foxp3 undergoes several definite post-translational modifications (PTMs), including acetylation, glycosylation, phosphorylation, ubiquitylation, and methylation. These PTMs not only elevate or mitigate the transcriptional activity of Foxp3 but also affect the stability and immunosuppressive function of Tregs. Various studies have shown that pharmacological targeting of enzymes involved in PTMs can significantly influence the PTMs of Foxp3; thus, it may influence the progression of cancers and/or autoimmune diseases. Overall, this review will help researchers to understand the advances in the immune-suppressive mechanisms of Tregs, the post-translational regulations of Foxp3, and the potential therapeutic targets and strategies to target the Tregs in TME to improve anti-tumor immunity.Copyright © 2023 Riaz, Huang and Pan.