Single-Cell Transcriptomic Profiling Reveals That Macrophage-Induced Angiogenesis Contributes to Immunotherapy Resistance in Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) ranks among the top causes of cancer-related mortality worldwide, and its complex tumor microenvironment (TME) contributes to poor responses to immunotherapy. Although PD-1/PD-L1 blockade has emerged as an effective treatment strategy, therapeutic resistance frequently limits its clinical benefit. Here, we uncover a distinct macrophage population associated with anti-PD-1 resistance in HCC. Single-cell transcriptomic profiling reveals an NFKBIZ⁺ M0 macrophage subset predominantly present in non-responders. Notably, these macrophages exhibit a hypoxia-induced phenotype characterized by the secretion of VEGFA and HBEGF, which cooperatively enhance tumor angiogenesis, alongside an elevated expression of the inflammatory chemokines

SUBMITTER: Pan X 

PROVIDER: S-EPMC12784835 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature