Midkine inhibition enhances anti-PD-1 immunotherapy in sorafenib-treated hepatocellular carcinoma via preventing immunosuppressive MDSCs infiltration.

ABSTRACT: Sorafenib, a multiple-target tyrosine kinase inhibitor, is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but provides limited benefits. Emerging evidences suggest that prolonged sorafenib treatment induces an immunosuppressive HCC microenvironment, but the underling mechanism is undetermined. In the present study, the potential function of midkine, a heparin-binding growth factor/cytokine, was evaluated in sorafenib-treated HCC tumors. Infiltrating immune cells of orthotopic HCC tumors were measured by flow cytometry. Differentially expressed genes in sorafenib-treated HCC tumors were evaluated by transcriptome RNA sequencing. The potential function of midkine were evaluated by western blot, T cell suppression assay, immunohistochemistry (IHC) staining and

SUBMITTER: Ding L 

PROVIDER: S-EPMC10008628 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature