Inhibiting B cells enhances the efficacy of STING agonism or immune checkpoint blockade in hepatocellular carcinoma.

ABSTRACT: Most patients with hepatocellular carcinoma (HCC) develop resistance to immune checkpoint blockade (ICB) or STING agonists despite their immune-stimulating activities. Here, we identify increased intratumoral B-cell infiltration as a mediator of acquired resistance. In HCC models with liver fibrosis in male mice, anti-PD-1 ICB or the STING agonist BMS-986301 increase intratumoral B-cell infiltration, circulating IL-10, and TIM-1⁺ B-cells, promoting tertiary lymphoid structure formation. B-cell depletion combined with ICB or STING agonism improves survival, and STING agonism inhibits distant metastasis. In addition, co-targeting STING and TIM-1 enhances B-cell differentiation and antigen presentation, reduces intratumoral TIM-1⁺ B-cells, and increases CD86 and MHC clas

SUBMITTER: Liu X 

PROVIDER: S-EPMC12686393 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature