Extracellular Vesicles Mediate B Cell Immune Response and Are a Potential Target for Cancer Therapy

Abstract

Extracellular vesicles (EVs) are increasingly understood to participate directly in many essential aspects of host antitumor immune response. Tumor- and immune-cell-derived EVs function in local and systemic contexts with roles in immune processes including cancer antigen conveyance, immune cell priming and activation, as well as immune escape. Current practice of cancer immunotherapy has de facto focused on eliciting T-cell-mediated cytotoxic responses. Humoral immunity is also known to exert antitumor effects, and B cells have been demonstrated to have functions that extend beyond antibody production to include antigen presentation and activation and modulation of T cells and innate immune effectors. Evidence of B cell response against tumor-associated antigens (TAAs) is observed in early stages of tumorigenesis and in most solid tumor types. It is known that EVs convey diverse TAAs, express antigenic-peptide-loaded MHCs, and complex with circulating plasma antitumoral autoantibodies. In this review, we will consider the relationships between EVs, B cells, and other antigen-presenting cells, especially in relation to TAAs. Understanding the intersection of EVs and the cancer immunome will enable opportunities for developing tumor antigen targets, antitumor vaccines and harnessing the full potential of multiple immune system components for next-generation cancer immunotherapies.

Role of Extracellular Vesicles in Autoimmune Pathogenesis

“…Indeed, EVs may be involved in the presentation of intracellular self-antigens to the immune system. Antigen-presenting cells (APCs) can undergo intracellular transfer and effective antigen delivery to autoantigen-specific T cells through EVs, which represents a highly efficient mechanism of antigen presentation (23)(24)(25). Additionally, many types of tissue-or humoral-derived EVs have been discovered to possess immunomodulatory or tolerogenic activities.…”

Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues

“…Polymorphisms in various genes can result in defective regulation or reduced threshold for lymphocyte activation, and environmental factors (e.g., infections, traumas) initiate or augment activation of self-reactive lymphocytes that have escaped control and that can react against auto-antigens [ 5 ]. A role for extracellular vesicles in the process of auto-antibody production has also been proposed [ 6 ].…”

Warburg’s Ghost—Cancer’s Self-Sustaining Phenotype: The Aberrant Carbon Flux in Cholesterol-Enriched Tumor Mitochondria via Deregulated Cholesterogenesis

“…Further investigations restricted the exosome nomenclature to vesicles of endosomal derivation based on the protein components within their membranes, or by the cargo enclosed within them, compared with extracellular microvesicles (sometimes called "ectosomes") shed from the plasma membranes of healthy, growing cells, whether of normal or pathological origin (Raposo and Stoorvogel, 2013). There remains nomenclature confusion over the biogenesis of shed membrane vesicles, which are referred to merely as extracellular vesicles (EV) (Kato et al, 2020).…”

“…Despite recent decades employing sophisticated membrane cholesterol imaging and other analytical techniques that have elucidated the roles and evolution of shed vesicles (whether exosomes or ectosomes) in intercellular trafficking, and their potential involvement in immune surveillance (Raposo and Stoorvogel, 2013;Record et al, 2014;Litvinov et al, 2018;Kato et al, 2020), cholesterol's organization in the cholesterol-rich lipid raft microdomains of the plasma membrane remains poorly understood (Schroeder et al, 2010). Evidence shows the distribution of cholesterol between lipid bilayer leaflets in plasma membranes is not equal, with the cytosol-facing leaflet cholesterol-enriched by as much as 40 mol% of the lipids in that leaflet (Mondal et al, 2009).…”