Advances and challenges in cancer immunotherapy targeting regulatory T cells

Regulatory T cells (Tregs) are important mediators of immune tolerance, but represent a major barrier to effective antitumor immunity in the tumor microenvironment (TME). Accumulating evidence indicates that intratumoral Treg enrichment is associated with immune evasion, tumor progression, and resistance to immunotherapy in many malignancies. This review systematically examines current strategies targeting Tregs in cancer, including antibody-mediated depletion (anti-CD25, anti-CTLA-4), immune checkpoint modulation, inhibition of Treg trafficking, and metabolic reprogramming approaches. We analyze mechanistic insights underlying Treg stability and suppressive function, including FOXP3-dependent transcriptional regulation, IL-2/STAT5 signaling, PI3K-Akt-mTOR pathway, and CD39/CD73-mediated adenosine production. Furthermore, we evaluate preclinical findings and emerging clinical data, highlighting the therapeutic efficacy, limitations, and immune-related side effects associated with Treg-targeted interventions. Although selective Treg modulation has proven promise for improving antitumor responses, systemic depletion poses giant dangers for immune dysregulation and autoimmunity. Therefore, future techniques should prioritize spatially limited and functionally precise targeting inside TME. Advances in single-cell sequencing, metabolic profiling, and precision immunotherapy structures offer new possibilities to refine Treg-focused cures and enhance medical results. Collectively, this evaluate gives a comprehensive mechanistic and translational framework for know-how Treg biology in most cancers and descriptions future directions for the development of safer and extra effective immunotherapeutic techniques.