Exosomes, Their Biogenesis and Role in Inter-Cellular Communication, Tumor Microenvironment and Cancer Immunotherapy

Jella, Kishore Kumar; Nasti, Tahseen H.; Li, Zhentian; Malla, Sudarshan; Buchwald, Zachary S.; Khan, Mohammad K.

doi:10.3390/vaccines6040069

Cited by 113 publications

(129 citation statements)

References 107 publications

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“…Exosomes function as a robust and intricate intercellular communication system, which is evolutionarily conserved down to gram negative bacteria [72,73]. TEX transmit malignant information in the form of proteins, RNAs, lipids, and metabolites that can reprogram recipient cells [74,75].…”

Section: Tumor-derived Exosomesmentioning

confidence: 99%

Immunoregulatory Potential of Exosomes Derived from Cancer Stem Cells

Clayton

Archard

Wagner

et al. 2020

Stem Cells and Development

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Head and neck squamous cell carcinomas (HNSCCs) are malignancies that originate in the mucosal lining of the upper aerodigestive tract. Despite advances in therapeutic interventions, survival rates among HNSCC patients have remained static for years. Cancer stem cells (CSCs) are tumor-initiating cells that are highly resistant to treatment, and are hypothesized to contribute to a significant fraction of tumor recurrences. Consequently, further investigations of how CSCs mediate recurrence may provide insights into novel druggable targets. A key element of recurrence involves the tumor's ability to evade immunosurveillance. Recent published reports suggest that CSCs possess immunosuppressive properties, however, the underlying mechanism have yet to be fully elucidated. To date, most groups have focused on the role of CSC-derived secretory proteins, such as cytokines and growth factors. Here, we review the established immunoregulatory role of exosomes derived from mixed tumor cell populations, and propose further study of CSC-derived exosomes may be warranted. Such studies may yield novel insights into new druggable targets, or lay the foundation for future exosome-based diagnostics.

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Section: Tumor-derived Exosomesmentioning

confidence: 99%

Immunoregulatory Potential of Exosomes Derived from Cancer Stem Cells

Clayton

Archard

Wagner

et al. 2020

Stem Cells and Development

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“…As discussed above, TDEs can exert regulatory influences on immune responses through both local and systemic effects, and can carry factors that stimulate or suppress immune responses. However, perhaps the most important systemic role of TDEs appears to reside in their ability to build new niches that facilitate the development of tumor metastasis . TDEs derived from metastatic melanoma cells can enhance metastasis formation by “educating” bone marrow progenitors and preparing a suitable niche to assist subsequent metastasis .…”

Section: Tde‐mediated Immune Suppressionmentioning

confidence: 99%

“…However, perhaps the most important systemic role of TDEs appears to reside in their ability to build new niches that facilitate the development of tumor metastasis. 174 TDEs derived from metastatic melanoma cells can enhance metastasis formation by "educating"…”

Section: Tdes In the Tumor Metastasismentioning

confidence: 99%

Tumor‐derived exosomes (TDEs): How to avoid the sting in the tail

Wan

Ning

Spiegel

et al. 2019

Medicinal Research Reviews

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Exosomes are abundantly secreted extracellular vesicles that accumulate in the circulation and are of great interest for disease diagnosis and evaluation since their contents reflects the phenotype of their cell of origin. Tumor‐derived exosomes (TDEs) are of particular interest for cancer diagnosis and therapy, since most tumor demonstrate highly elevated exosome secretion rates and provide specific information about the genotype of a tumor and its response to treatment. TDEs also contain regulatory factors that can alter the phenotypes of local and distant tissue sites and alter immune cell functions to promote tumor progression. The abundance, information content, regulatory potential, in vivo half‐life, and physical durability of exosomes suggest that TDEs may represent a superior source of diagnostic biomarkers and treatment targets than other materials currently under investigation. This review will summarize current information on mechanisms that may differentially regulate TDE biogenesis, TDE effects on the immune system that promote tumor survival, growth, and metastasis, and new approaches understudy to counteract or utilize TDE properties in cancer therapies.

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“…Therefore, exosomes contain specific proteins and nucleic acids and represent their parent cell status and functions at the time of formation [13][14] . Among many subtypes of exosomes, immunogenic exosomes with an intrinsic payload of MHC class I and II molecules and other co-stimulatory molecules are able to mediate immune responses [15][16] , which opens up opportunities for the development of novel cancer vaccines and delivery in immunotherapy [17][18][19][20][21][22][23][24][25][26] .…”

Section: Introductionmentioning

confidence: 99%

Microfluidic On-demand Engineering of Exosomes towards Cancer Immunotherapy

Zhao

McGill

2018

Preprint

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Extracellular Vesicles (EVs), particularly exosomes (30-150 nm), are an emerging delivery system in mediating cellular communications, which have been observed for priming immune responses by presenting parent cell signaling proteins or tumor antigens to immune cells. Therefore, preparation of antigenic exosomes that can play therapeutic roles, particularly in cancer immunotherapy, is emerging. However, standard benchtop methods (e.g., ultracentrifugation and filtration) lack the ability to purify antigenic exosomes specifically among other microvesicle subtypes, due to the non-selective and timeconsuming (>10 h) isolation protocols. Exosome engineering approaches, such as the transfection of parent cells, also suffer from poor yield, low purity, and time-consuming operations. In this paper, we introduce a streamlined microfluidic cell culture platform for integration of harvesting, antigenic modification, and photo-release of surface engineered exosomes in one workflow, which enables the production of intact, MHC peptide surface engineered exosomes for cytolysis activation.The PDMS microfluidic cell culture chip is simply cast from a 3D-printed mold. The proof-of-concept study demonstrated the enhanced ability of harvested exosomes in antigen presentation and T cell activation, by decorating melanoma tumor peptides on the exosome surface (e.g., gp-100, MART-1, MAGE-A3). Such surface engineered antigenic exosomes were harvested in real-time from the on-chip culture of leukocytes isolated from human blood, leading to much faster cellular uptake. The activation of gp100-specific CD8 T cells which were purified from the spleen of 2 Pmel1 transgenic mice was evaluated using surface engineered exosomes prepared from muring antigen presenting cells. Antigen-specific CD8 T cell proliferation was significantly induced by the engineered exosomes compared to native, non-engineered exosomes. This microfluidic platform serves as an automated and highly integrated cell culture device for rapid, and real-time production of therapeutic exosomes that could advance cancer immunotherapy.

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Exosomes, Their Biogenesis and Role in Inter-Cellular Communication, Tumor Microenvironment and Cancer Immunotherapy

Cited by 113 publications

References 107 publications

Immunoregulatory Potential of Exosomes Derived from Cancer Stem Cells

Immunoregulatory Potential of Exosomes Derived from Cancer Stem Cells

Tumor‐derived exosomes (TDEs): How to avoid the sting in the tail

Microfluidic On-demand Engineering of Exosomes towards Cancer Immunotherapy

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