@article{Li2026, 
author = {Na Li and Dexue Tian},
title = {Targeting tumor-infiltrating regulatory T cells based on immunometabolism},
year = {2026},
journal = {Cancer Biology & Medicine},
volume = {23},
number = {2},
pages = {186-200},
keywords = {Tumor-infiltrating regulatory T cells, immunometabolism, immune checkpoint inhibitors, CD8+ T cells, tumor microenvironment},
url = {https://www.sciopen.com/article/10.20892/j.issn.2095-3941.2025.0645},
doi = {10.20892/j.issn.2095-3941.2025.0645},
abstract = {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.}
}