Unleashing the Power of immune Checkpoints: A new strategy for enhancing Treg cells depletion to boost antitumor immunity

Abstract

Regulatory T (Treg) cells, immunosuppressive CD4⁺ T cells, can impede anti-tumor immunity, complicating cancer treatment. Since their discovery, numerous studies have been dedicated to understand Treg cell biology, with a focus on checkpoint pathways' role in their generation and function. Immune checkpoints, such as PD-1/PD-L1, CTLA-4, TIGIT, TIM-3, and OX40, are pivotal in controlling Treg cell expansion and activity in the tumor microenvironment (TME), affecting their ability to suppress immune responses. This review examines the complex relationship between these checkpoints and Tregs in the TME, and how they influence tumor immunity. We also discuss the therapeutic potential of targeting these checkpoints to enhance anti-tumor immunity, including the use of immune checkpoint blockade (ICB) therapies and novel approaches such as CCR8-targeted therapies. Understanding the interaction between immune checkpoints and Treg cells can lead to more effective immunotherapeutic strategies, such as combining CCR8-targeted therapies with immune checkpoint inhibitors, to improve patient outcomes in cancer treatment.

Keywords: CCR-8; Immune checkpoint blockade; Immunotherapy; Regulatory T cells; Tumor microenvironment.