Dendritic Cell-Derived Exosomes in Cancer Immunotherapy

Abstract

Exosomes are nanoscale vesicles released by diverse types of cells for complex intercellular communication. Numerous studies have shown that exosomes can regulate the body’s immune response to tumor cells and interfere with the tumor microenvironment (TME). In clinical trials on dendritic cell (DC)-based antitumor vaccines, no satisfactory results have been achieved. However, recent studies suggested that DC-derived exosomes (DEXs) may be superior to DC-based antitumor vaccines in avoiding tumor cell-mediated immunosuppression. DEXs contain multiple DC-derived surface markers that capture tumor-associated antigens (TAAs) and promote immune cell-dependent tumor rejection. These findings indicate the necessity of the further development and improvement of DEX-based cell-free vaccines to complement chemotherapy, radiotherapy, and other immunotherapies. In this review, we highlighted the recent progress of DEXs in cancer immunotherapy, particularly by concentrating on landmark studies and the biological characterization of DEXs, and we summarized their important role in the tumor immune microenvironment (TIME) and clinical application in targeted cancer immunotherapy. This review could enhance comprehension of advances in cancer immunotherapy and contribute to the elucidation of how DEXs regulate the TIME, thereby providing a reference for utilizing DEX-based vaccines in clinical practice.

A comprehensive insight into the immunomodulatory role of MSCs‐derived exosomes (MSC‐Exos) through modulating pattern‐recognition receptors (PRRs)

“…In this scenario, it becomes evident that the identical exosomes can be internalized by dissimilar cell types (specifically, DCs and cancer cells) through disparate mechanisms (phagocytosis by DCs and endocytosis by cancer cells). These differential mechanisms align with these cells' unique roles and requisites within the contexts of immune response orchestration and tumor advancement, serving as a pertinent illustration of the contextual diversity inherent in exosome uptake mechanisms 30 …”

ExoDS: a versatile exosome-based drug delivery platform to target cancer cells and cancer stem cells

“…NKG2D ligands are often overexpressed in cancer and infected cells but are rarely expressed in normal tissues. The expression of NKG2DLs on the surface of tumor cells is induced by transcriptional upregulation due to cellular or genomic stress, and while it is usually expressed in most epithelial-derived tumor cells, it is rarely detected in healthy adult tissues ( Munich et al, 2012 ; Luo et al, 2023 ). Human mDCs have the ability to kill tumor cells via TRAIL, FasL expression, or TNF-α, perforin, and granzyme secretion.…”

“…Exosomes are also more resistant to immunomodulatory events in vivo ( Pitt et al, 2016 ). Therefore, exosome-based cell-free therapy is rapidly emerging as the next generation of cancer therapy ( Dutta, 2021 ; Dutta and Paul, 2022 ; Luo et al, 2023 ).…”