What is the role of exosomes in the immune response?

It has been widely reported that exosomes can carry miRNAs that are functional in recipient cells, thus mediating cell-to-cell communication. Therefore, miRNAs may play a protective role by attenuating inflammation or modulating the immune response. The 21st century has witnessed significant advances in the field of extracellular vesicle (VE) research, including significant advances toward the definition of standard criteria for the separation and detection of electric vehicles. The recent recognition that electric vehicles have the potential to function as biomarkers or as therapeutic tools has attracted even more attention to his study.

Given this progress, it is timely to have a complete and up-to-date overview of the functions of electric vehicles in the immune system. This review summarizes the roles of electric vehicles in the basic processes of innate and adaptive immunity, including inflammation, antigen presentation, and B and T cell development and activation. It also highlights key advances related to the deciphering of the functions of electric vehicles in antimicrobial defense and in allergic, autoimmune and anti-tumor immune responses. It ends by focusing on the relevance of electric vehicles for immunotherapy and vaccination, and paying attention to ongoing or recently completed clinical trials that aim at harnessing the therapeutic potential of electric vehicles.

Exosomes are released from 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 content.

Biomolecular. 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). The pathways related to NF-b activation and TLR cascades differ between the exosomal mRNAs of virgin cells and those of 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 innate immune system plays a crucial role in defending the host against viral and microbial infections. Exosomes constitute a subset of extracellular vesicles (EVs) that can be released by nearly all cell types.

Because of their ability to protect the payload from degradation and prevent the immune system from recognizing and then eliminating them, exosomes efficiently transport functional components to recipient cells. Accumulated evidence has recently demonstrated that exosomes derived from tumor cells, host cells, and even bacteria and parasites mediate communication between the invader and innate immune cells and, therefore, play an irreplaceable role in the dissemination of pathogens and molecules derived from donor cells, modulating the host's innate immune responses. In this review, we describe the current understanding of electric vehicles (focusing primarily on exosomes) and summarize and discuss their crucial roles in determining innate immune responses. In addition, we analyze the potential of using exosomes as biomarkers and cancer vaccines in diagnostic and therapeutic applications. Since inflammatory T cell responses are one of the important factors in the development of multiple sclerosis, the use of Treg-derived exosomes to inhibit their function may be useful; studies reveal that exosomes produced from Treg in people with multiple sclerosis have fewer immunomodulatory effects compared to healthy people.

Exosomes can be used in adoptive immune cell therapy, at immune checkpoints, in cancer vaccines and in therapies against oncolytic viruses. As a new generation of natural biological carriers at the nanoscale, exosomes have attracted the attention of scholars in the field of tumor therapy. A microfluidic chip is used to evaluate EpCAM-positive circulating exosomes with plasma exosomes. Unlike the studies mentioned above that describe how exosomes derived from tumor cells promote inflammation, this work shows how exosomes can have different functions depending on the type of cell with which they interact.

Additional research and modification of exosomes will help solve the above problems and promote the clinical application of exosomes as immunomodulatory molecules and carriers for drug delivery. Originally, it was discovered that B cell exosomes used major histocompatibility complex (MHC) class I and II proteins on their surface to perform antigen presentation work, which others have expanded to demonstrate the antitumor effect of immune cell exosomes (recently reviewed in). NK cell exosomes express the DNAX-1 accessory molecule (DNAM) on their surface, allowing exosomes to integrate with the tumor cell membrane by binding to PVR and nectin. Exosome biogenesis involves the intersection of a variety of complex mechanisms, and exosomes carry a variety of molecules, such as proteins, nucleic acids, and lipids.

Exosomes produced by adipose-derived stromal cells (ASC) can also be used in prostate cancer therapy. As the exosome burden is highly dependent on the release of host cells, changes, if any, in the tissue microenvironment are reflected in the exosomal load. In some cases, exosome attachment is sufficient to exert modifications on the target cell, but in other cases, the exosome must be internalized in addition to the attachment. For example, CDS-derived exosomes can carry tumor antigens to lymph nodes and then transfer them between different subsets of CDs to stimulate specific immunity and regulate the host's immune response, while Treg cell-derived exosomes can induce immune tolerance.

Liquid biopsy of exosomes isolated from patients with prostate cancer revealed that exosomes are enriched with genes that are characteristic of prostate cancer, such as the androgen receptor, kallikreins (KLK), the cyclin-dependent kinase 1A inhibitor (CDKN1A), KLK10, JUN and B2M (microglobulin beta2). A CAR T-inspired platform based on exosomes designed with dendritic cell antibodies that feed on antigens for precise solid tumor therapy.