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

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.