Regulatory T cells in renal cell carcinoma: tumor-promoting mechanisms and emerging therapeutic strategies.

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.