Zhang Jun,Wu Xiaohou,Chen Gang,Luo Chunli.Renal cell carcinoma-derived exosomes induce monocytes to differentiate into PD-L1 myeloid derived suppressor cells in vitro[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(02):172-174.
Zhang Jun,Wu Xiaohou,Chen Gang,Luo Chunli.Renal cell carcinoma-derived exosomes induce monocytes to differentiate into PD-L1 myeloid derived suppressor cells in vitro[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(02):172-174.DOI:
Objective To assess the process of renal cell carcinoma-derived exosomes (RCC-exo) inducing human peripheral blood monocytes to differentiate into myeloid-derived suppressor cells (MDSCs) and determine the expression of programmed death ligand 1 (PD-L1) in the differentiated cells. Methods RCC-exo were isolated and purified by ultrafiltration and sucrose gradient centrifugation
and characterized by transmission electron microscopy. Ficoll density gradient centrifugation was used to isolate peripheral blood mononuclear cells (PBMC) from healthy donor
and monocytes were amplified and purified from PBMC
which characterized by inverted microscopy. The obtained monocytes were induced by RCC-exo for 48 h
and those without treatment served as control. Flow cytometry were used to analyze the impairment of monocytes
the presence of MDSCs and the expression of PD-L1. Results Attached monocytes were round or round-like in shape
with a few pseudopod processes. The yield rate was 83.5%
and 90.0% obtained cells were alive. Compared with control group
RCC-exo obviously impaired monocytes [(39.93±16.51)% vs (12.87±2.43)%
P0.05)]
and promoted myeloid cells differentiation into MDSCs [(8.91±0.21)% vs (3.19±0.91)%
P0.05]. Among the obtained cells
the percentage of PD-L1 MDSCs was (88.93±8.57)%
significantly higher than that of control group [(44.53±5.35)%
and the cells differentiate into MDSCs with significantly increased PD-L1. PD-L1 and PD-1 interaction may be one of the pathways that MDSCs suppress T cells immune response.