Immunotherapy is a promising treatment for metastatic melanoma. However, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-L1 antibody, has lower response rate in patients. Dendritic cells play a critical role as central orchestrators of the immune response. Dendritic cell-derived exosomes might inherit some special functions from dendritic cells and exert these functions in vivo. We find that microRNAs and proteins are present in dendritic cell-derived exosomes and could affect other immature dendritic cells. Then, we induced melanomas in C57BL/6 mice and then intravenously injected dendritic cell-derived exosomes into mice, observing that the combination of dendritic cell-derived exosomes enhanced the efficacy of anti-PD-L1 antibody, but treatment with either dendritic cell-derived exosomes or anti-PD-L1 antibody alone, did not. These were suggested that combination of dendritic cell-derived exosomes and anti-PD-L1 antibody will significantly improve overall survival time.