Objective:The aim of the present study was to investigate the effects of 5-fluorouracil (5-Fu) and oxaliplatin on the function and activation pathways of mouse dendritic cells (DCs),and to clarify whether 5-Fu/oxaliplatin combined with the CD1d-MC38/α-galactosylceramide (α-GC) tumor vaccine exhibits synergistic effects on the treatment of colon cancer in mice.Methods:The combination of the Toll like receptor (TLR) ligands and/or 5-Fu/oxaliplatin was added into myeloid-derived DCs in vitro culture.DC phenotypic changes were detected by flow cytometry,and the secretion of DC cytokines was detected by cytometric bead array (CBA).A MC38 mouse colon cancer model was constructed and the DCs were isolated from the spleen,tumor tissue and lymph nodes following intraperitoneal injection of 5-Fu/oxaliplatin.The cell phenotypes were detected by flow cytometry.The tumor infiltrating leukocytes,splenocytes and lymph node cells were co-cultured with the dead MC38 tumor cells,and the secretion levels of interferon-γ (IFN-γ) were detected.5-Fu/oxaliplatin combined with our previously developed CD1d-MC38/α-GC tumor vaccine was used to inhibit the growth of MC38 colon cancer in mice,and the tumor growth rate and survival time were recorded.Results:5-Fu/oxaliplatin exerted no significant effect on the expression of the stimulating phenotypes of DCs in vitro,while it could reduce the expression of programmed death ligand 1/2 (PD-L1/L2) and promote interleulin-12 (IL-12) secretion by DCs.Furthermore 5-Fu/oxaliplatin was beneficial to the differentiation of T-helper 1 (Th1) cells.5-Fu/oxaliplatin further enhanced the stimulating phenotypic expression of DCs in tumor bearing mice,decreased PD-L1/L2 expression,and specifically activated the lymphocytes.The CD 1 d-MC38/α-GC tumor vaccine combined with 5-Fu/oxaliplatin could exert a synergistic role that resulted in a significant delay of the tumor growth rate,and an increase in the survival time of tumor bearing mice.Conclusions:5-Fu/oxaliplatin decreased the expression of the DC inhibitory phenotypes PD-L l/L2,promoted DC phenotypic maturation in tumor bearing mice,activated the lymphocytes of tumor bearing mice,and exerted synergistic effects with the CD 1 d-MC38/α-GC colon cancer tumor vaccine.