PLAUR⁺ Neutrophils Drive Anti-PD-1 Therapy Resistance in Patients with Hepatocellular Carcinoma by Shaping an Immunosuppressive Microenvironment.

ABSTRACT: Hepatocellular carcinoma (HCC) is characterized by an immunosuppressive tumor microenvironment (TME) that limits the efficacy of immune checkpoint inhibitors. However, the role of distinct neutrophil subsets within the TME in mediating tumor resistance to immunotherapy remains poorly understood. Here, the present study reveals that the urokinase-type plasminogen activator receptor (PLAUR)⁺ neutrophils are enriched in immunotherapy non-responders and correlate with poor prognosis. Through multi-omics analyses of clinical cohorts and preclinical models, PLAUR⁺ neutrophils identify as a pivotal driver of immunotherapy resistance by shaping an immunosuppressive TME. Mechanistically, spatial transcriptomics and single-cell RNA sequencing reveal that PLAUR⁺ neutr

SUBMITTER: Liu S 

PROVIDER: S-EPMC12520528 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature