Renal Cell Carcinoma-derived Exosomes Induced Monocytes To PD-L1~+Myeloid Derived Suppressor Cells In Vitor

Objective: To assess the effects of renal cell carcinoma-derivedexosomes induce human peripheral blood induce to myeloid-derivedsuppressor cells and expression the coinhibitory molecules of Programmeddeath ligand1(PD-L1).Materials and methods: Renal cell carcinoma-derived exosomeswere isolated and purified by ultrafihration and sucrose gradientcentrifugation. Ficoll density gradient centrifugation of peripheral bloodmononuclear cells (PBMC) from Healthy donor and monocytes wereamplified and purified from PBMC, which characterized by Invertedmicroscope. monocytes were induced by renal cell carcinoma-derivedexosomes for48hours, then flow cytometry were used to analyze theimpairment of monocytes,the expression of Myeloid-derived suppressorcells (MDSCs) and coinhibitory molecules of Programmed death ligand1(PD-L1).Results: Monocytes are impaired by renal cell carcinoma-derivede xosomes [(39.93±16.51)%VS (12.87±2.43)%,(P<0．05)] and renal cell carcinoma-derived exosomes promote myeloid cells differentiation intoMyeloid derived suppressor cells[(8.91±0.21)%VS(3.19±0.91)%,(P<0．05)] and the subet ofPD-L1+MDSCs[(88.93±8.57)%VS (44.53±5.35)%,(P<0．05)].Conclusions: Monocytes were impaird by tumor exosomes.Monocytes induced by tumor exosomes, the expression of MDSCssignificantly increased and PD-L1molecules on MDSCs significantlyup-regulated, which suggest that immune suppression may be exist in renalcell carcinoma through MDSCs which is stimulated by tumor exosomes,PD-L1and PD-1interaction may be one of the pathways that MDSCssuppress T cells Immune response.