Extracellular vesicles at the crossroad between cancer progression and immunotherapy: focus on dendritic cells
Extracellular vesicles at the crossroad between cancer progression and immunotherapy: focus on dendritic cells
Blog Article
Abstract Extracellular vesicles (EVs) are nanosized heat-stable vesicles released by virtually all cells in the body, including tumor cells and tumor-infiltrating dendritic cells (DCs).By carrying molecules from originating cells, EVs work as cell-to-cell communicators in both homeostasis and cancer but may also represent valuable therapeutic and diagnostic tools.This review focuses on the role of tumor-derived EVs (TEVs) in the modulation of DC functions and on the therapeutic potential of both tumor- and DC-derived EVs in the context of immunotherapy and DC-based vaccine design.TEVs were originally characterized for their capability to transfer tumor antigens to DCs but are currently regarded as mainly immunosuppressive because of kt196 torque converter the expression of DC-inhibiting molecules such as PD-L1, HLA-G, PGE2 and others.However, TEVs may still represent a privileged system to deliver antigenic material to DCs upon appropriate engineering to reduce their immunosuppressive cargo or increase immunogenicity.
DC-derived EVs are more promising than tumor-derived EVs since they expose antigen-loaded MHC, costimulatory molecules and NK cell-activating ligands in the absence of an immunosuppressive cargo.Moreover, DC-derived EVs possess several advantages as compared to cell-based drugs such as a higher cga 200 to cga 510 adapter antigen/MHC concentration and ease of manipulation and a lower sensitivity to immunosuppressive microenvironments.Preclinical models showed that DC-derived EVs efficiently activate tumor-specific NK and T cell responses either directly or indirectly by transferring antigens to tumor-infiltrating DCs.By contrast, however, phase I and II trials showed a limited clinical efficacy of EV-based anticancer vaccines.We discuss that the future of EV-based therapy depends on our capability to overcome major challenges such as a still incomplete understanding of their biology and pharmacokinetic and the lack of standardized methods for high-throughput isolation and purification.
Despite this, EVs remain in the limelight as candidates for cancer immunotherapy which may outmatch cell-based strategies in the fullness of their time.