Dendritic cell-derived exosome (DEX) therapy for digestive system cancers; recent advances and future prospect

Exosomes are extracellular vehicles (EVs) that are generated by a variety of cells and have been the subject of many investigations [1], [2], [3]. Initially, exosomes were thought to be cell wastes, with the theory that cells generated them to preserve homeostasis. Exosomes range in size from 30 to 150 nm, as first discovered via electron microscopy in 1946. It has now been discovered that EVs, which are typically released in both states of health and disease, are essential for cellular communication and are released by various cells [3]. Exosomes can have paracrine, endocrine, and autocrine impacts depending on the markers and ligands that are present on their surface. Similar to other cells, immune cells are capable of secreting exosomes, which act as vesicles to communicate with neighboring cells. Exosomes produced by immune system cells (IEXs) elicit diverse responses, including modulating the transcription of multiple genes and controlling the generation of cytokines [4]. Exosomes have a role in immune system cell-to-cell communication, antigen presentation, T cell activation and polarization, natural killer cells (NK cells), immunological suppression, and a number of anti-inflammatory actions.

The strongest antigen-presenting cells in the body are dendritic cells (DCs) [5]. DCs prime B cells and T cells, both killer and helper types, with antigens (Fig. 1). The DC-based vaccination has become a key tactic in cancer immunotherapy during the last ten years [6]. There are several reports of improved survival and minor vaccination-related adverse reactions from phase I or II clinical trials using DC-based immunotherapy to treat multiple cancers. DC-based immunotherapy has certain drawbacks. For instance, it is challenging to define the molecular makeup of DCs and is subject to change [7]. Soluble immunosuppressive inflammatory mediators secreted by cancer cells have the ability to transform immature DCs into tolerogenic DCs, which in turn may stimulate Treg cells. Live DCs require local production, which presents quality control challenges, and are inconvenient for storing [8]. DC-derived exosomes (DEXs or dexosomes) were originally created as a substitute method for cancer vaccines in order to overcome such challenges [8]. Dex have a variety of molecules, including costimulatory and adhesion molecules, MHC class I and class II, that are required for antigen presentation [9], [10]. In vivo, tumor peptide-pulsed Dex activate antigen-specific cytotoxic T lymphocytes (CTLs) to eliminate or inhibit the development of pre-existing murine cancers in a manner that relies on MHC and CD8+ T cell [11], [12]. DEXs-based cancer vaccines have been hailed as the better alternative cell-free therapeutic vaccines than DC vaccines for treating digestive system malignancies because of their resilience to tumor immunosuppression. Current research on DEX's cancer vaccines for treatment of digestive system malignancies alongside possible future paths will be discussed in this review.

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