Merck

MicroRNAs in Tumor Exosomes Drive Immune Escape in Melanoma.

Cancer immunology research (2019-12-21)
Virginie Vignard, Maureen Labbé, Nadège Marec, Gwennan André-Grégoire, Nicolas Jouand, Jean-François Fonteneau, Nathalie Labarrière, Delphine Fradin
ABSTRACT

MicroRNAs (miRNA), 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 melanoma-derived exosomes in CD8+ T cells and showed that these exosomes downregulate T-cell responses through decreased T-cell receptor (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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® microRNA Mimic, hsa-miR-498
Sigma-Aldrich
MISSION® microRNA Mimic, hsa-miR-181a
Sigma-Aldrich
MystiCq® microRNA cDNA Synthesis Mix
Sigma-Aldrich
MystiCq® microRNA® SYBR® Green qPCR ReadyMix, Formulation for miRNA RT-qPCR on iQ Bio-Rad platforms
Sigma-Aldrich
MISSION® microRNA Mimic, hsa-miR-122
Sigma-Aldrich
MISSION® microRNA Mimic, hsa-miR-181b