Cabozantinib enhances the anti-tumor immune effect of PD-L1 monoclonal antibody by regulating CD8+T cells
Objective To explore the effect and molecular mechanism of cabozantinib combined with programmed cell death-ligand 1(PD-L1)monoclonal antibody in the treatment of hepatocellular carcinoma(HCC).Methods Subcutaneous tumor-bearing model was constructed using mouse hepatoma cells Hepa1-6.Model mice were divided into the control group,cabozantinib treatment group,PD-L1 monoclonal antibody treatment group,and cabozantinib+PD-L1 monoclonal antibody treatment group according to the intervention methods.The tumor growth rate of mice in each group was analyzed;the proportion of T cell infiltration in tumor tissues of mice in each group was detected by flow cytometry.Multicolor immunofluorescence was used to analyze the infiltration of T cells in tumor tissues of mice in each group.The expression levels of cytokines in the serum of mice in each group were detected by enzyme-linked immunosorbent assay(ELISA).Results The inhibitory effect of the cabozantinib+PD-L1 monoclonal antibody on the tumorigenic ability of hepatoma cells in vivo was significantly stronger than that of the cabozantinib or PD-L1 monoclonal antibody.The results of flow cytometry and multicolor immunofluorescence detection showed that the proportion of CD8+T cells in the tumor tissues of the cabozantinib+PD-L1 monoclonal antibody treatment group was significantly higher than that of the cabozantinib or PD-L1 monoclonal antibody treatment group.The results of enzyme-linked immunosorbent assay(ELISA)showed that the expression levels of TNF-α,IFN-γ and IL-6 in the serum of mice in the cabozantinib+PD-L1 monoclonal antibody treatment group were significantly higher than those in the cabozantinib or PD-L1 monoclonal antibody treatment group.The results of the in vivo tumorigenesis experiment showed that the CD8 antibody could antagonize the inhibitory effect of cabozantinib combined with PD-L1 on the tumorigenic ability of mouse hepatoma cells.Conclusion Cabozantinib may enhance the anti-hepatocellular carcinoma effect of PD-L1 by recruiting CD8+T cells,and is expected to become a new strategy to enhance the effect of anti-tumor immunotherapy.
万方数据
维普
