Regulatory T cells in breast cancer drivers of immune suppression and targets for immunotherapy

Breast cancer remains one of the most prevalent malignancies and a leading cause of cancer-related death in women worldwide. Increasing evidence indicates that regulatory T cells (Tregs), a specialized subset of CD4⁺ T cells, play a central role in breast cancer initiation, progression, and therapeutic response by shaping an immunosuppressive tumor microenvironment. Tregs originate from both thymic and peripheral differentiation pathways and are characterized by the expression of FoxP3, CD25, CTLA-4, PD-1, and other immune regulatory molecules. In breast cancer, Tregs accumulate within tumor tissues and peripheral blood through chemokine-mediated recruitment, local expansion, and phenotypic conversion, where they suppress antitumor immunity via IL-2 deprivation, inhibitory cytokine secretion, cytolytic activity, metabolic disruption, and checkpoint signaling. Their enrichment is closely associated with tumor immune escape, invasion, metastasis, and poor prognosis. Moreover, emerging therapeutic strategies targeting Tregs, including immune checkpoint blockade, anti-CCR4 antibodies, vaccines, and pathway-modulating agents, have shown promise in restoring antitumor immunity. This review summarizes the origins, phenotypic features, immunosuppressive mechanisms, and clinical relevance of Tregs in breast cancer, and discusses the opportunities and challenges of Treg-centered immunotherapeutic strategies.