A resveratrol derivative RVX-208 inhibits PD-1/PD-L1 to restrain non-small cell lung cancer as an immunotherapy

Immunotherapies, particularly anti-PD-1 antibodies, have emerged as standard first-line treatments for non-small cell lung cancer (NSCLC). RVX-208, derived from resveratrol, has recently completed Phase III clinical trials for atherosclerosis in the United States. In this study, we demonstrate for the first time that RVX-208 suppresses lung cancer growth in vivo by enhancing T cell-mediated immunity notably rather than directly suppressing lung cancer cell proliferation. Mechanically, RVX-208 interfered with janus kinase 2 (JAK2) to reduce its phosphorylation, reduced both the programmed death-1 (PD-1) expression in T lymphocytes and programmed death-ligand 1 (PD-L1) expression in lung cancer cells, thereby inhibiting the growth of lung cancer cells co-cultured with T lymphocytes in vitro. Furthermore, RVX-208 enhanced the anti-tumor activity of anti-PD-1 antibody in lung cancer cells that were co-cultured with lymphocytes in vitro. Consistent with these findings, RVX-208 treatment also reduced PD-1 levels in T cells from tumor bearing mice in vivo. Collectively, these results identify RVX-208 as a promising small-molecule immunotherapeutic agent for the treatment of lung cancer.