Li Zuolei, Ma Jing, Xu Mengdie, Duan Yi, Huang Conggai, Dai Qiong, Yang Zhihui
School of Basic Medical Sciences of Southwest Medical University, Luzhou 646000, Sichuan, China; Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China; Precision Pathology Diagnosis for Serious Diseases Key Laboratory of LuZhou, Luzhou, Sichuan, China.
Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China; Precision Pathology Diagnosis for Serious Diseases Key Laboratory of LuZhou, Luzhou, Sichuan, China.
Int Immunopharmacol. 2025 Oct 10;163:115322. doi: 10.1016/j.intimp.2025.115322. Epub 2025 Aug 5.
Renal cell carcinoma (RCC) exhibits an immunogenic paradox: while inherently immunogenic, it actively recruits regulatory T cells (Tregs) into the tumor microenvironment (TME) to enable immune evasion. Tregs suppress immunity through direct cellular contact and inhibitory cytokine secretion, promoting RCC growth, metastasis, and angiogenesis. Clinically, Treg infiltration correlates with advanced tumor stage, therapy resistance, and poor prognosis. Emerging strategies to reprogram the TME include CD25 blockade, metabolic modulators targeting Treg stability, and cell therapies or CRISPR-based Treg modulation, all of which show preclinical promise. However, clinical translation faces challenges like on-target toxicity, compensatory checkpoint activation, and patient stratification. This review synthesizes Tregs' pathogenic role in RCC, dissects their molecular mechanisms, evaluates current therapeutic approaches, and analyzes translational challenges in modulating Treg activity.
肾细胞癌（RCC）表现出一种免疫原性悖论：虽然其本质上具有免疫原性，但它会主动将调节性T细胞（Tregs）招募到肿瘤微环境（TME）中以实现免疫逃逸。Tregs通过直接细胞接触和抑制性细胞因子分泌来抑制免疫，促进RCC的生长、转移和血管生成。临床上，Treg浸润与肿瘤晚期、治疗抵抗和不良预后相关。重新编程TME的新兴策略包括CD25阻断、靶向Treg稳定性的代谢调节剂以及细胞疗法或基于CRISPR的Treg调节，所有这些在临床前研究中都显示出前景。然而，临床转化面临着诸如靶向毒性、代偿性检查点激活和患者分层等挑战。本综述综合了Tregs在RCC中的致病作用，剖析了其分子机制，评估了当前的治疗方法，并分析了调节Treg活性的转化挑战。
