Skip to Main content Skip to Navigation
Journal articles

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.
Complete list of metadatas

Cited literature [52 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02426329
Contributor : Elizabeth Bernardo <>
Submitted on : Thursday, January 2, 2020 - 10:51:25 AM
Last modification on : Thursday, February 20, 2020 - 2:28:02 PM
Document(s) archivé(s) le : Monday, April 6, 2020 - 7:06:23 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Citation

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⟩

Share

Metrics

Record views

225