Modulating Treg stability to improve cancer immunotherapy

Immunosuppressive regulatory T cells (Tregs) provide a main mechanism of tumor immune evasion. Targeting Tregs, especially in the tumor microenvironment (TME), continues to be investigated to improve cancer immunotherapy. Recent studies have unveiled intratumoral Treg heterogeneity and plasticity, furthering the complexity of the role of Tregs in tumor immunity and immunotherapy response. The phenotypic and functional diversity of intratumoral Tregs can impact their response to therapy and may offer new targets to modulate specific Treg subsets. In this review we provide a unifying framework of critical factors contributing to Treg heterogeneity and plasticity in the TME, and we discuss how this information can guide the development of more specific Treg-targeting therapies for cancer immunotherapy.