Lactylation-Driven NUPR1 Promotes Immunosuppression of Tumor-Infiltrating Macrophages in Hepatocellular Carcinoma.

ABSTRACT: While checkpoint immunotherapy effectively mobilizes T-cell responses against tumors, its success in hepatocellular carcinoma (HCC) is frequently undermined by immunosuppressive myeloid cells within the tumor microenvironment. This study investigates the role of nuclear protein 1 (NUPR1), a gene prominently expressed in tumor-associated macrophages (TAMs), in mediating this suppression and influencing immunotherapy outcomes. Through comprehensive analysis of single-cell RNA sequencing (scRNA-seq) datasets and functional assays in vitro and in vivo, NUPR1 is identified as a critical regulator within TAMs. The upregulation of NUPR1 is associated with enhanced M2 macrophage polarization and increased expression of immune checkpoints PD-L1 and SIRPA, resulting in CD8+ T cell exhaustion and a d

SUBMITTER: Cai J 

PROVIDER: S-EPMC12120759 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature