Combined SEP and anti-PD-L1 antibody produces a synergistic antitumor effect in B16-F10 melanoma-bearing mice

The increased PD-L1 induces poorer prognosis in melanoma. The treatment with PD-1/PD-L1 antibodies have a low response rate. The combination immunotherapies are the encouraging drug development strategy to receive maximal therapeutic benefit. In this study, we investigated the enhanced antitumor and immunomodulatory activity of combined SEP and alpha PD-L1 in B16-F10 melanoma-bearing mice. The results shown that combined SEP and alpha PD-L1 presented significant synergistic antitumor effects, increased the frequency of CD8(+) and CD4(+)T cells in spleen and tumor, cytotoxic activity of CTL in spleen, and IL-2 and IFN-gamma levels in splenocytes and tumor. The combination treatment also produced synergistic increase in P-ERK1/2 level in spleen. Immunohistochemistry shown that SEP induced the PD-L1 expression in melanoma tissue possibly by promoting IFN-gamma excretion, which led to the synergistic anti-tumor effects of alpha PD-L1 and SEP. Furthermore, in the purified T lymphocyte from the naive mice, the combination of SEP and alpha PD-L1 had more potent than SEP or alpha PD-L1 in promoting T lymphocyte proliferation and cytokines secretion including IL-2 and IFN-gamma, at least partially by activating MEK/ERK pathway. Our study provides the scientific basis for a clinical trial that would involve combination of anti-PD-L1 mAb and SEP for sustained melanoma control.