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Review
. 2023 Jan 6:10:1080925.
doi: 10.3389/fcell.2022.1080925. eCollection 2022.

Immunosuppressive functions of melanoma cell-derived exosomes in plasma of melanoma patients

Affiliations
Review

Immunosuppressive functions of melanoma cell-derived exosomes in plasma of melanoma patients

Theresa L Whiteside. Front Cell Dev Biol. .

Abstract

Tumor-derived exosomes (TEX) are a subset of small extracellular vesicles (sEV) present in all body fluids of patients with cancer. In plasma of patients with metastatic melanoma, numbers of exosomes produced by melanoma cells called MTEX are elevated. To study the role of MTEX in melanoma progression, immunoaffinity-based separation of MTEX from total plasma exosomes was performed. The surface of MTEX was decorated by various checkpoint inhibitory proteins, and upon coincubation with immune recipient cells, MTEX suppressed anti-tumor functions of these cells. MTEX emerge as a major mechanism of immune suppression in melanoma and thus might play a role in promoting melanoma progression.

Keywords: exosomes; immune capture; immune suppression; melanoma; melanoma cell-derived exosomes (MTEX); small extracellular vesicles.

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Conflict of interest statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Transmission electron microscopy images of sEV from a healthy donor’s plasma (left) and from a melanoma patient’s plasma (right).
FIGURE 2
FIGURE 2
Protein levels in total plasma exosomes of melanoma patients or HDs and in isolated MTEX. In (A), total exosome protein (TEP) levels in plasma of HDs or melanoma patients. In (B), the total MTEX/TEP ratio for all patients vs. patients with NED or with progressive disease following oncological therapy. In (C), protein levels in MTEX obtained from plasma of NED patients or melanoma patients with metastases (i.e., progressive disease following oncological.
FIGURE 3
FIGURE 3
Measurement of TEX-induced phenotypic and functional changes in T cells following their co-incubation with TEX or sEV from cancer plasma. Following co-incubation at optimized doses for different time periods depending on the assay, T cells were tested for the vesicle uptake or entry into the cytosol or for changes in the surface protein profile, in growth and apoptosis levels or in mRNA transcription. Vertical stipled lines indicate that inhibitors of the T cell-TEX crosstalk can be used to block T cell-TEX interactions.

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