Exosomes mediate communication between different types of immune cells in the innate and adaptive immune systems. The interaction of the exosome with different cell types induces a simultaneous activation of primary and secondary immune cells. Exosomes, small extracellular vesicles, mediate intercellular communication by transferring their cargo, including DNA, RNA, proteins and lipids, from one cell to another. In particular, in the immune system, they have protective functions.
However, in cancer, exosomes acquire new immunosuppressive properties that cause immune cell dysregulation and the immune escape of tumor cells, promoting cancer progression and metastasis. Therefore, current research focuses on regulating exosome levels for immunotherapeutic interventions. In this review, we analyze the role of exosomes in the immunomodulation of lymphoid and myeloid cells, and their use as immunostimulating agents to elicit specific cytotoxic responses against the tumor. The exosomes are released by pathogens and host cells.
They modulate stimulatory or suppressive effects on the innate immune system through exosome-mediated intercellular communications. They are crucial in immune regulation, including antigen presentation, immune activation, immune suppression, and immune tolerance. Its immunoactivating or suppressive function depends primarily on the source of the exosomes and their biomolecular content. Exosomes derived from healthy human plasma samples contain several RNA species, such as mRNA and non-coding regulatory RNAs, within these circulating vesicles (17-1).
Pathways related to NF-b activation and TLR cascades differ between exosomal mRNAs in virgin cells and those in cells stimulated by LPS, indicating significant changes in innate and adaptive immune processes. Exosomes also carry critical soluble mediators, such as cytokines. Upon stimulation with LPS, RAW 264.7 mouse macrophages showed elevated levels of cytokines, predominantly chemokines. Ten of the 16 cytokines secreted by RAW 264.7 cells stimulated with LPS came from cell-derived exosomes (20). The development of effective therapies for the treatment of cancer requires a better understanding of the tumor's extracellular environment and a dynamic interaction between tumor cells, immune system cells and the tumor stroma.
There is increasing evidence to suggest that extracellular vesicles play an important role in this interaction. Extracellular vesicles are nanometer-sized membrane-bound vesicles secreted by various cell types that facilitate intracellular communication by transferring proteins, various lipids, and nucleic acids, especially miRNAs, between cells. Extracellular vesicles play different roles in the regulatory functions of the immune system, such as the presentation of antigens and the activation or suppression of immune cells. Achieving therapeutic intervention by targeting extracellular vesicles is a today's crucial area of research.
Therefore, a deeper understanding of the biology of exosomes and the molecular mechanism of immune regulation is likely to provide significant insight into the therapeutic intervention that uses extracellular vesicles to combat this terrible disease. This review describes recent updates on immune regulation by extracellular vesicles in cancer progression and their potential use in cancer treatment. Tumor microenvironmental cytokines attached to cancer exosomes determine their uptake by cells that express cytokine receptors and their biodistribution. Cancer-derived exosomal miR-651 as a diagnostic marker restricts resistance to cisplatin and acts directly against ATG3 in cervical cancer.
Last but not least, exosomes have the ability to cross the blood-brain barrier without further modification (7), while lipid nanoparticles may require a specific chemical modification (80). In addition, host proteins and miRNA are modified during MTB infection and can facilitate MTB immune evasion. During an infection, exosomes loaded with the MHC II peptide are secreted by IECs, taken up by antigen-presenting cells and induce effective activation of T cells. Exosomes are small electrical vehicles of endosomal origin released by the exocytosis of multivesicular bodies (MVB) and amphysomes.
Plasmacytoid dendritic cells cross virgin CD8 T cells by transferring the antigen to conventional dendritic cells through exosomes. The exosome-coated nanocomposites showed better long-term retention, biocompatibility and penetration behavior than those of free Ce6. Therefore, the exosome plays an important vector role in facilitating signaling communication between cells by using its contents to regulate various cellular functions. The exosomes produced by IFNgam-stimulated MSCs reduced demyelination, decreased neuroinflammation, and up-regulated the number of regulatory, CD4, CD25, FOXP3 and regulatory T cells in the spinal cord. Therefore, exploring the possible effects of innate immune cell exosomes on infection by the MTB bacteria is useful for developing new vaccines.
and treatments. In their neoadjuvant clinical trial, the researchers also discovered that levels of the immunosuppressive cytokine were significantly higher in EXVs isolated from the serum of patients with BC who overexpressed HER2 and who did not respond to drug treatment aimed at HER2 than in those who experienced a total or partial response. Therefore, exosomes can suppress the function of activated macrophages instead of acting as an immune stimulator.
