Immune modulation and anti-tumor effects mediated by T-cell immunological synaptosomes

Abstract

T cells have short and actin-rich membrane protrusions called microvilli, which serve as sensors for detecting cognate antigens presented by major histocompatibility complex molecules on antigen-presenting cells. Upon T cell activation, microvilli are released from the cell body as extracellular vesicles, called T cell immunological synaptosomes (TISs), which contain membrane receptors that play crucial roles in T cell activation, proximal signaling molecules, and cytokines that can activate other immune cells. In this study, we investigated the immunomodulatory and anti-tumor effects of TIS in vivo. In vivo administration of TISs resulted in their efficient uptake by APCs, such as macrophages and dendritic cells, leading to the induction of immune responses. Notably, in the MC38 colon cancer model, TIS treatment significantly reduced tumor burden and improved survival compared to control groups. Moreover, TIS-mediated anti-tumor immunity persisted for several months. These findings suggest that TIS represents a novel immune modulator and a promising strategy for cancer immunotherapy.