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MicroRNAs in Tumor Exosomes Drive Immune Escape in Melanoma

Abstract : MicroRNAs (miRNAs), small noncoding RNAs that regulate gene expression, exist not only in cells but also in a variety of body fluids. These circulating miRNAs could enable intercellular communication. miRNAs are packaged in membrane-encapsulated vesicles, such as exosomes, or protected by RNA-binding proteins. Here we report that miRNAs included in human melanoma exosomes regulate the tumor immune response. Using microscopy and flow cytometry, we demonstrate that CD8+ T cells internalize exosomes from different tumor types even if these cells do not internalize vesicles as readily as other immune cells. We explored the function of melanomaderived exosomes in CD8+ T cells and showed that these exosomes downregulate T-cell responses through decreased TCR signaling and diminished cytokine and granzyme B secretions. The result reduces the cells’ cytotoxic activity. Using mimics, we found that miRNAs enriched in exosomes— such as Homo sapiens (hsa)-miR-3187-3p, hsa-miR-498, hsa-miR-122, hsa-miR149, and hsa-miR- 181a/b —regulate TCR signaling and TNFα secretion. Our observations suggest that miRNAs in melanoma-derived exosomes aid tumor immune evasion and could be a therapeutic target.
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Submitted on : Thursday, January 2, 2020 - 10:51:25 AM
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Virginie Vignard, Maureen Labbé, Nadège Marec, Gwennan André-Grégoire, Nicolas Jouand, et al.. MicroRNAs in Tumor Exosomes Drive Immune Escape in Melanoma. Cancer Immunology Research, American Association for Cancer Research, 2019, canimm.0522.2019, Epub ahead of print. ⟨10.1158/2326-6066.CIR-19-0522⟩. ⟨inserm-02426329⟩



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