%0 Journal Article
%T Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma
%A Agata Cova
%A Ambra Gualeni
%A Angela De Laurentiis
%A Antonello Villa
%A Barbara Vergani
%A Elena Casiraghi
%A Elisabetta Vergani
%A Eriomina Shahaj
%A Filippo De Braud
%A Flavio Arienti
%A Licia Rivoltini
%A Lorenza Di Guardo
%A Luca Lalli
%A Luigi Mariani
%A Mara Cossa
%A Matteo Dugo
%A Monica Rodolfo
%A Paola Filipazzi
%A Peter Altevogt
%A Roberta Sulsenti
%A Roberto Patuzzo
%A Valentina Bollati
%A Veronica Huber
%A Viktor Fleming
%A Viktor Umansky
%A Viviana Vallacchi
%A Xiaoying Hu
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI98060
%X 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
%U https://www.jci.org/articles/view/98060