We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma.
- Authors
Huber, Veronica; Vallacchi, Viviana; Fleming, Viktor; Xiaoying Hu; Cova, Agata; Matteo Dugo; Shahaj, Eriomina; Sulsenti, Roberta; Vergani, Elisabetta; Filipazzi, Paola; De Laurentiis, Angela; Lalli, Luca; Di Guardo, Lorenza; Patuzzo, Roberto; Vergani, Barbara; Casiraghi, Elena; Cossa, Mara; Gualeni, Ambra; Bollati, Valentina; Arienti, Flavio
- 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.
- Subjects
TUMORS; MICRORNA; IMMUNOTHERAPY; MELANOMA treatment; SUPPRESSOR cells; CANCER patients; MONOCYTES
- Publication
Journal of Clinical Investigation, 2018, Vol 128, Issue 12, p5505
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI98060