摘要The immune checkpoint blockade(ICB)approach in cancer therapy involves the disruption of immune checkpoint inhibitory signals on tumor-specific CD8+T cells,thereby reinstating the immune activity of CD8+T cells and yielding therapeutic efficacy.However,due to the co-expression of immune checkpoint molecules,such as CTLA-4 and PD-1 on tumor-infiltrating Tregs(TI-Tregs)and conventional T cells(Tconvs),immune checkpoint inhibitors(ICIs)inadvertently amplify the immunosuppressive activity of Tregs while targeting CD8+T cells,which contributes to the failure of immune therapy.Conventional strategies targeting Tregs,including ICI/conventional kinase and chemokine/chemokine receptor blockade,generally induce systemic Treg depletion,which triggers autoimmune diseases.Thus,achieving high selectivity and specificity in targeting TI-Tregs is of paramount importance in mitigating adverse immunologic reactions.Targeting metabolism-based TI-Tregs has been shown to enhance target precision,providing potential for the development of adjunctive immunotherapeutic strategies.This article explores the reciprocal interaction between TI-Tregs and the tumor microenvironment(TME),elucidating metabolic reprogramming,while envisioning plausible high-selectivity targets for TI-Tregs without compromising systemic immune homeostasis and immune reactivity of effector T cells.