Blocking interaction between SHP2 and PD-1 denotes a opportunity for developing PD-1 inhibitors

ABSTRACT: Small molecular PD-1 inhibitors are lacking in current immuno-oncology clinic. PD-1/PD-L1 antibody inhibitors currently approved for clinical usage block interaction between PD-L1 and PD-1 to enhance cytotoxicity of CD8+ cytotoxic T lymphocyte (CTL). Whether other steps along the PD-1 signaling pathway can be targeted remains to be determined. Here, we report that methylene blue (MB), an FDA approved chemical for treating methemoglobinemia, potently inhibits PD-1 signaling. MB enhances the cytotoxicity, activation, cell proliferation and cytokine secreting activity of CTL inhibited by PD-1. Mechanistically, MB blocks interaction between Y248 phosphorylated immunoreceptor tyrosine-based switch motif (ITSM) of human PD-1 and SHP2. MB enables activated CTL to shrink PD-L1 expressing tumor all

SUBMITTER: Dr. Liang Chen 

PROVIDER: S-SCDT-EMM-2019-11571 | biostudies-other |

REPOSITORIES: biostudies-other