PD-L1 antibody enhanced β-glucan antitumor effects via blockade of the immune checkpoints in a melanoma model.

In the tumor microenvironment (TME), one of the major functions of tumor-recruited CD11b cells are the suppression of the T-cell-mediated anti-tumor immune response. β-glucan could convert the phenotype of tumor-recruited CD11b cells from the suppressive to the promotive, and enhanced their anti-tumor effects. However, β-glucan could enhance the PD-1/PD-L1 expression on CD11b cells, while PD-1 could inhibit macrophage phagocytosis and PD-L1 could induce a co-inhibitory signal in T-cells and lead to T-cell apoptosis and anergy. These protumor effects may be reversed by PD-1/PD-L1 block therapy. In the present study, we focused on the efficacy of β-glucan anti-tumor therapy combined with anti-PD-L1 mAb treatment, and the mechanism of their synergistic effects could be fully verified. We verified the effect of β-glucan (i.e., inflammatory cytokine secretion of TNF-α, IL-12, IL-6, IL-1β and the expression of immune checkpoint PD-1/PD-L1) in naïve mouse peritoneal exudate CD11b cells. In our mouse melanoma model, treatment with a PD-L1 blocking antibody with β-glucan synergized tumor regression. After treatment with β-glucan and anti-PD-L1 mAb antibody, tumor infiltrating leukocyte (TILs) not only showed a competent T-cell function (CD107a, perforin, IL-2, IFN-γ and Ki67) and CTL population, but also showed enhanced tumor-recruited CD11b cell activity (IL-12, IL-6, IL-1β and PD-1). This effect was also verified in the peritoneal exudate CD11b cells of tumor-bearing mice. PD-1/PD-L1 blockade therapy enhanced the β-glucan antitumor effects via the blockade of tumor-recruited CD11b cell immune checkpoints in the melanoma model.