Combination CXCR4 and PD-1 Blockade Enhances Intratumoral Dendritic Cell Activation and Immune Responses Against Hepatocellular Carcinoma.

ABSTRACT: Immune checkpoint inhibitors have revolutionized the treatment of unresectable hepatocellular carcinoma (HCC), but their impressive efficacy is seen in just a fraction of patients. One key mechanism of immunotherapy resistance is the paucity of dendritic cells (DC) in liver malignancies. In this study, we tested combination blockade of PD-1 and CXCR4, a receptor for CXCL12, a pleiotropic factor that mediates immunosuppression in tumors. Using orthotopic grafted and autochthonous HCC models with underlying liver damage, we evaluated treatment feasibility and efficacy. In addition, we examined the effects of treatment using immunofluorescence, flow cytometric analysis of DCs in vivo and in vitro, and RNA sequencing. The combination anti-CXCR4 and anti-PD-1 therapy was safe and significantly

SUBMITTER: Morita S 

PROVIDER: S-EPMC11788650 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature