Regulatory T Cells in Cancer Immunotherapy: From Tumor Microenvironment Dynamics to Bispecific Antibody Approaches

Regulatory T (Treg) cells are crucial in maintaining immune homeostasis and preventing autoimmunity1. However, within the tumor microenvironment (TME), Tregs shift their role towards immune suppression. In cancer, the immune system develops resistance, contributing to a suppressive TME. The TME plays a vital role in tumorigenesis2, and tumor-infiltrating lymphocytes (TILs) are key components of this environment. These lymphocytes consist of various cell types, including natural killer (NK) cells, CD8+ cytotoxic T cells, CD4+ helper T cells and regulatory T cells. Various interactions and immune responses occur between tumor cells and neighboring cells through the circulatory and lymphatic systems. These interactions include the upregulation of immune checkpoint molecules, the secretion of immunosuppressive cytokines, and alterations in the metabolic environment of effector T cells, among other mechanisms. This facilitates the tumor cells to evade immune detection, escape the immune system, and promote tumor growth and survival. In recent years, immunotherapy has emerged as one of the most promising treatments for cancer, significantly transforming the therapeutic landscape of cancer care. By harnessing the power of the immune system, immunotherapies target and combats tumor cells. Regulatory T cells have become key targets in the development of new immunotherapeutic strategies due to their pivotal role in immune evasion of cancer cells3. In this review, we delve into the molecular characteristics and immunosuppressive mechanisms of Tregs in cancer, with a focus on key molecules CD25 (IL-2 receptor α chain) and TIGIT (T cell immunoreceptor with Ig and ITIM domains), which play significant roles in tumor immune evasion. We also discuss the potential of bispecific antibodies (BsAbs) as a therapeutic treatment for tumor by selectively targeting Tregs markers (CD25 and TIGIT) within the tumor microenvironment.