Inhibiting B-cell-mediated Immunosuppression to Enhance the Immunotherapy Efficacy in Hepatocellular Carcinoma.

ABSTRACT:

Background

Immunotherapy is efficacious in hepatocellular carcinoma (HCC), but the benefits are limited to a minority of patients. Most HCC patients show resistance to immune checkpoint blockade (ICB). Agonists of the stimulator of interferon genes (STING), potent immune stimulators, showed limited effectiveness. Using preclinical models, we studied the mechanisms of resistance to ICB and STING agonism.

Methods

Murine HCA-1 and RIL-175 HCCs were orthotopically grown in mice with underlying liver fibrosis, to mimic the presentation of human HCC. Established tumors were treated with a STING agonist (BMS-986301) or anti-PD1 ICB, and mice were followed to evaluate safety and efficacy, as well as the mechanisms of treatment resistance by RNA sequencing, flow cytometry, and immuno

SUBMITTER: Liu X 

PROVIDER: S-EPMC12047993 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature