Crosstalk Between Extracellular Vesicles and Regulatory T Cells Across Cancers: From Interaction to Therapeutic Potential

Di Liu,1,* Zhixiong Hao,2,* Guangpeng He,2 Ye Huang3 1Department of Anesthesiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, People’s Republic of China; 2Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People’s Republic of China; 3Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ye Huang, Email [email protected] Guangpeng He, Email [email protected]: Regulatory T cells (Treg cells) play a crucial role in maintaining immune tolerance and regulating immune responses, especially in cancer, where their immunosuppressive function is highly significant. Treg cells accumulate in the tumor microenvironment (TME), interact with tumor cells and other immune cells, and suppress anti-tumor immunity through various mechanisms, including secretion of immunosuppressive cytokines, direct contact with target cells, and depletion of key nutrients and signaling molecules. Regulating Treg cells has become a novel approach for enhancing cancer immunotherapy. Extracellular vesicles (EVs) are small vesicles with a lipid bilayer membrane secreted by all cells and play an important role in tumor biology as communication mediators by transmitting proteins, RNA, and other bioactive molecules in TME. In the past years, an increasing amount of research has uncovered the effects of EVs on Treg in TME, greatly enriching our understanding of Treg in tumor progression. Additionally, due to the potential of EVs as “natural nanoparticles” for drug and gene delivery, targeting Treg via an EV-delivery system has become a hotspot. Therefore, we comprehensively summarized the updates on the effects of EVs on Treg in TME and EV-related therapy for tumor treatment.Keywords: regulatory T cells, extracellular vesicle, tumor microenvironment, immunotherapy