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MHC class I–peptide complexes displayed on dendritic cell–derived exosomes (DEX) are specialized extracellular vesicles that function as cell-free mediators of the adaptive immune response (Zitvogel et al., 1998). These vesicles are secreted by dendritic cells and harbor a high density of MHC class I and II molecules, costimulatory proteins (CD80, CD86), and adhesion molecules (ICAM-1), which allow them to interact directly with T cells or transfer their cargo to other antigen-presenting cells (André et al., 2004; Biomedicines, 2025). In cancer therapy, DEX are utilized as vaccines by loading them with tumor-associated antigens to induce specific CD8+ cytotoxic T lymphocyte (CTL) responses (Frontiers in Immunology, 2024). While early clinical trials demonstrated safety and some biological activity in patients with melanoma and non-small cell lung cancer, the efficacy of first-generation DEX was limited, leading to the development of 'second-generation' IFN-gamma-stimulated DEX (Exosome-RNA, 2016). These advanced formulations aim to enhance T cell priming and NK cell activation, often in combination with immunomodulatory chemotherapy like cyclophosphamide to counteract tumor-induced immunosuppression (MDPI, 2025).
Dendritic cell-derived exosomes (DEX) facilitate the activation of the adaptive immune system through the presentation of antigenic peptides via MHC class I molecules. They can directly stimulate CD8+ T cells or transfer their MHC-peptide complexes to other dendritic cells (a process known as cross-dressing) to enhance antigen presentation (André et al., 2004). Additionally, DEX can be internalized by recipient antigen-presenting cells, where the cargo is reprocessed and presented on the host cell's own MHC molecules (Frontiers in Immunology, 2024).
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