The Flavonoid Apigenin Inhibits Inducible Programmed Death Ligand 1 Expression by Breast Cancer Cells

Abstract

Programmed death ligand 1 (PD-L1) is a T cell inhibitory molecule expressed by activated T cells and antigen presenting cells, as well as by various tumor types. PD-L1 expression is believed to contribute to immune evasion by breast cancer cells. The goal of this investigation was to determine the effect of the phytochemical apigenin on PD-L1 expression by several breast cancer cell lines. Apigenin inhibited both IFN-?- and IFN-?-induced upregulation of PD-L1 by various breast cancer cell lines but did not affect constitutive PD-L1 expression. Apigenin also inhibited IFN-?-induced STAT1 phosphorylation. Apigenin-mediated reduction of IFN-?-induced PD-L1 expression by breast cancer cells increased Jurkat T cell proliferation in the presence of breast cancer cells. These data show that apigenin inhibits IFN-induced PD-L1 expression by breast cancer cells. Therefore, apigenin may act as an immunomodulator that increases the vulnerability of breast cancer cells to anti-tumor immune responses.