Understanding the role of regulatory T cell-derived small extracellular vesicles in suppression of anti-tumor immune response: Key to advancing cancer immunotherapy.

Abstract

Regulatory T cells (Tregs) represent a distinct T cell subpopulation crucial for preserving immune homeostasis. Their primary function is to facilitate self-tolerance and suppress other immune responses, achieved through multifaceted mechanisms, including the secretion of extracellular vesicles (EVs) such as exosomes, which effectively modulate the activity of other innate and adaptive immune cells. Treg-derived extracellular vesicles (Treg-EVs) are minute, membrane-bound vesicles containing specific biological molecules, comprising proteins, nucleic acids, and lipids. Upon transfer to target cells, these molecules exert diverse effects on immune responses. The Treg-mediated immune suppression process encompasses several contact-dependent and contact-independent mechanisms. These encompass the expression of various inhibitory receptors, such as CTLA-4, PD-1, CD39, and CD73, which serve to regulate the immune response. Furthermore, Tregs exhibit the capacity to directly eliminate target cells through the expression of perforin and granzyme B. Additionally, Tregs produce immunosuppressive cytokines that play a pivotal role in maintaining immune system equilibrium. Studying the impact of Treg-derived exosomes on the immune system in cancer is crucial for advancing cancer research and treatment. Understanding these interactions is vital for unraveling the potential implications for cancer development and progression.