Programmed death-ligand 1 monoclonal antibody enhances humoral immunity elicited by sensitized B cells with DC vaccine targeting CSCs
Objective:To explore whether the programmed death-ligand 1(PD-L1)monoclonal antibody can enhance humoral immunity elicited by sensitized B cells with DC vaccine targeting CSCs.Methods:A B16-F10 melanoma mouse model was established.Mice were treated with PBS,ALDHhigh CSC-DC vaccine with IgG,ALDHhigh CSC-DC vaccine,PD-L1 monoclonal antibody,or ALDHhigh CSC-DC vaccine plus PD-L1 monoclonal antibody,respectively.The survival time and tumor volume of the mice were recorded.At the end of the experiment,tumors from each group of mice were collected,and a single tumor cell suspension was subjected to ALDEFLUOR staining to detect the proportion of CSCs.Flow cytometry was used to detect the expression of PD-1 on B cells in the spleens of mice from each group.Additionally,antibody binding assays and complement-dependent cytotoxicity(CDC)assays were conducted to assess the ability of antibodies in the cul-tured supernatant of B cells to bind and lyse ALDHhigh CSCs.Results:Compared to the solo treatment group,the combined treatment of PD-L1 monoclonal antibody with ALDHhigh CSC-DC vaccine significantly inhibited tumor growth and prolonged the survival time of mice.The expression level of PD-1 in activated B lymphocytes in the combined treatment group was significantly decreased to 6.5％.Antibody binding assays suggested that antibodies in the cultured supernatant of B cells from the combined treatment group could bind more specifically to ALDHhgh CSCs(15.7％)compared to the ALDHhigh CSC-DC vaccine solo treatment(11.3％).Furthermore,CDC assay results showed that the B cell cultured supernatant from the combined treatment group specifically lysed ALDHhigh CSCs.Conclusion:The PD-L1 monoclonal antibody can significantly enhance the humoral immune response elicited by sensitized B cells with DC vaccine targeting ALDHhigh CSCs.
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