期刊
CANCER IMMUNOLOGY RESEARCH
卷 8, 期 2, 页码 255-267出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-19-0522
关键词
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资金
- Ligue contre le cancer - Comite 22
- Canceropole Grand Ouest - AOStructurant - ExomiR
- Vaincre le Melanome
- National Research Agency via the investment of the future program [ANR-11-LABX-0016-01]
- Ligue contre le cancer - Comite 29
- Ligue contre le cancer - Comite 35
- Ligue contre le cancer - Comite 44
- Ligue contre le cancer - Comite 56
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 TNF alpha secretion. Our observations suggest that miRNAs in melanoma-derived exosomes aid tumor immune evasion and could be a therapeutic target.
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