Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma.
J Clin Invest
; 128(12): 5505-5516, 2018 12 03.
Article
em En
| MEDLINE
| ID: mdl-30260323
ABSTRACT
The accrual of myeloid-derived suppressor cells (MDSCs) represents a major obstacle to effective immunotherapy in cancer patients, but the mechanisms underlying this process in the human setting remain elusive. Here, we describe a set of microRNAs (miR-146a, miR-155, miR-125b, miR-100, let-7e, miR-125a, miR-146b, miR-99b) that are associated with MDSCs and resistance to treatment with immune checkpoint inhibitors in melanoma patients. The miRs were identified by transcriptional analyses as being responsible for the conversion of monocytes into MDSCs (CD14+HLA-DRneg cells) mediated by melanoma extracellular vesicles (EVs) and were shown to recreate MDSC features upon transfection. In melanoma patients, these miRs were increased in circulating CD14+ monocytes, plasma, and tumor samples, where they correlated with the myeloid cell infiltrate. In plasma, their baseline levels clustered with the clinical efficacy of CTLA-4 or programmed cell death protein 1 (PD-1) blockade. Hence, MDSC-related miRs represent an indicator of MDSC activity in cancer patients and a potential blood marker of a poor immunotherapy outcome.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Melanoma Experimental
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RNA Neoplásico
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Leucócitos Mononucleares
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MicroRNAs
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Células Supressoras Mieloides
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Imunoterapia
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Itália