Abstract: Objective To investigate the killing effect of dendritic cells (DC) co-cultured with cytokine induced killer (CIK) cells on human osteosarcoma cells. Methods The peripheral blood mononuclear cells were isolated from healthy volunteers, the DC and CIK were prepared and co-cultured at a ratio of 5∶1. CCK-8 assay and flow cytometry were used to detect the effects of DC-CIK on the proliferation and apoptosis of human osteosarcoma HOS cells. The model of transplanted tumor in nude mice was established to observe the effect of DC-CIK on the growth of transplanted tumor. Results The results of flow cytometry showed that the percentage of CD83+ and CD86+ positive cells in mature DC was higher than that in immature DC (P=0.009, 0.006). The percentage of CD3+CD8+ and CD3+CD56+ positive cells in DC-CIK co-culture group was higher than that in CIK group (P=0.004, 0.004). After co-cultured with DC-CIK, the proliferation ability of HOS cells was inhibited and the apoptosis ability was enhanced (P<0.05). The expression of PD-L1 was significantly down-regulated (P=0.006). In nude mice model, DC-CIK co-culture could inhibit the growth of HOS cell-induced transplanted tumor (P=0.008). Conclusions DC-CIK co-culture can inhibit the proliferation and induce apoptosis of human osteosarcoma HOS cells, and its mechanism may be related to the targeted regulation of PD-1/PD-L1 signaling pathway.

Key words: Osteosarcoma, Dendritic cells, Cytokine-induced killer cells, Apoptosis, Proliferation, PD-1/PD-L1 signaling pathway