Harnessing extracellular vesicle-mediated crosstalk between T cells and cancer cells for therapeutic applications

Omar M Budayr; Brian Miller; Juliane Nguyen

doi:10.1016/j.jconrel.2024.12.011

Harnessing extracellular vesicle-mediated crosstalk between T cells and cancer cells for therapeutic applications

J Control Release. 2024 Dec 8:S0168-3659(24)00853-8. doi: 10.1016/j.jconrel.2024.12.011. Online ahead of print.

Authors

Omar M Budayr¹, Brian Miller², Juliane Nguyen³

Affiliations

¹ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, Division of Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: brian_c_miller@med.unc.edu.
³ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: julianen@email.unc.edu.

PMID: 39657892
DOI: 10.1016/j.jconrel.2024.12.011

Abstract

Small extracellular vesicles (EVs) are a diverse group of lipid-based particles that are ≤200 nm in diameter and contain an aqueous core. EVs have been shown to mediate intercellular communications between a wide array of immune cells; the downstream effects are diverse and have potential implications for the development of novel immunotherapeutic treatments. Despite a high volume of studies addressing the role EVs play in the immune system, our understanding of the crosstalk between T cells and cancer cells remains limited. Here, we discuss how EVs derived from cancer cells modulate T cell functions and conversely, how T cell derived EVs are crucial in modulating adaptive immune functions. In the context of cancer, tumor derived EVs (TD-EVs) halt T cell-mediated immunity by interfering with effector functions and enhancing regulatory T cell (Treg) functions. In contrast, EVs derived from effector T cells can serve to stimulate anticancer immunity, curbing metastasis and tumor growth. These findings highlight important aspects of how EVs can both mediate the therapeutic effects of T cells as well as impair T cell-mediated immunity. This calls for a deeper understanding of EV-mediated effects in order to advance them as next-generation therapeutics and nanocarriers.

Keywords: CAR T derived EVs; CD8+ derived EVs; T cell derived EVs; T cell exosomes; Tumor derived EVs.