Type I MET inhibitors cooperate with PD-1 blockade to promote rejection of hepatocellular carcinoma.

ABSTRACT: Blockade of the immune checkpoints programmed death-1 (PD-1) and cytotoxic lymphocyte antigen 4 has improved outcomes for patients with hepatocellular carcinoma (HCC), yet most still fail to achieve objective clinical benefit. MET plays key roles in both HCC tumorigenesis and immunosuppressive conditioning; however, inhibition of MET causes upregulation of PD-ligand 1 (PD-L1) suggesting the use of these inhibitors in the context of PD-1 blockade. We sought to investigate across the Hepa1-6, HCA-1 and diethylnitrosamine (DEN) models of HCC whether the combination of more specific type I versus more pleiotropic type II MET inhibitors would confer superior outcomes in combination with PD-1 blockade. While MET inhibition demonstrated cooperativity with αPD-1 across all three models, the type I

SUBMITTER: DeAzevedo R 

PROVIDER: S-EPMC11529525 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature