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Objective To investigate the inhibitory effect of myeloid-derived suppressor cells (MDSCs) activated by exosomes derived from Renca cells on the proliferation and killing activity of renal cancer antigen-specific cytotoxic T lymphocytes (CTLs) in vitro. Methods Exosomes derived from Renca cells were purified by ultracentrifugation, and exosome-induced activation of MDSCs was detected using flow cytometry. Mouse dendritic cells (DCs) and CD8+ T cells were isolated to prepare DC-activated renal cancer antigen-specific CTLs. Magnetic beads were used to sort out MDSCs activated by the exosomes, and fluorescence staining with carboxyfluorescein diacetate succinimidyl ester (CFSE) and flow cytometry were performed to assess the inhibitory effect of activated MDSCs on the proliferation of CTLs. MDSCs, CTLs and Renca cells were co-cultured in vitro, and the inhibitory effect of exosomes-activated MDSCs on the killing activity of CTLs was observed using LDH release assay. Results Renca cell-derived exosomes effectively induced the aggregation of MDSCs. We successfully isolated DCs from the mice and obtained DC-activated renal cancer antigen-specific CTLs. Compared with the CTLs cultured alone or in the presence of unactivated MDSCs, the CTLs co-cultured with exosomes-activated MDSCs showed a significantly lower proliferation index and a lower killing rate against Renca cells (P < 0.05). Conclusion MDSCs activated by Renca cell-derived exosomes can inhibit the proliferation and lower the cell-killing efficiency of renal cancer antigen-specific CTLs in vitro, suggesting a significant role of MDSCs in immune escape of renal cancer.