Víctor Calvo and Manuel Izquierdo, Researchers at the Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), have published an exhaustive review that addresses the generation of extracellular vesicles by T lymphocytes and CAR-T cells and their possible therapeutic uses against Cancer.
and Manuel Izquierdo
, researchers at the Instituto de Investigaciones Biomédicas Alberto Sols (IIBM)
Joint Center and the Universidad Autónoma de Madrid (UAM)
have explained in detail the biological relevance of extracellular vesicles (EV) derived from T lymphocytes and from chimeric antigen receptor T cells (CAR-T). The authors explain that EVs are a highly diverse group of extracellular vesicles released by almost all cell types and involved in intercellular communication. This is due to the fact that they deliver proteins, lipids and other molecules to the target cells, inducing signals in them that subsequently trigger biological responses in the target cells. While EVs are secreted basally by many cell types, secretion of EVs is induced by stimulation of the T cell antigen receptor (TCR) in T lymphocytes and CAR in CAR-T cells. These EVs have their own TCR and CAR for the antigen, and contain several bioactive molecules, including several proapoptotic proteins (granzymes, perforins, etc.) that induce cell death of the target cell whose antigen is recognized by the TCR/CAR. Therefore, these EVs are specifically directed against target cells such as tumor cells that present the antigen recognized by the TCR/CAR, which makes EVs ideal candidates for therapy against tumor cells without the need to infuse the EV-producing cells. In this review, the molecular mechanisms that control the generation of EVs by T lymphocytes and CAR-T cells and some cancer therapeutic approaches for these EVs are analyzed. For more details please refer to: T Lymphocyte and CAR-T Cell-Derived Extracellular Vesicles and Their Applications in Cancer Therapy.
The figure shows the extracellular vesicles in the immune synapse. In a mature immune synapse (IS) produced by T cell receptor (TCR) stimulation via the peptide-MHC complex (pMHC) on the APC and the interaction of accessory molecules (such as Intercellular Adhesion Molecule 1—ICAM1—with Lymphocyte function-associated antigen 1—LFA-1) F-actin is reduced at the cSMAC, the central region of the IS. F-actin accumulates at the distal SMAC (dSMAC), and F-actin around the centrosome depolymerizes. These F-actin reorganization processes, acting in a coordinated manner, may assist centrosome traffic towards the IS and the simultaneous convergence of MVB towards the F-actin depleted area in the cSMAC, facilitating MVB fusion at the cSMAC, and the subsequent exosome secretion carrying TCR and proapoptotic molecules in the synaptic cleft. In addition, shedding vesicles emerging from the plasma membrane and containing TCR are represented at the synaptic cleft. Both exosomes containing miRNA and shedding vesicles are engulfed by APC and provide biological responses in APC.