SGMS2+ macrophages enhance NR4A3hi NK cell infiltration to improve prognosis and PD-1 treatment efficacy in hepatocellular carcinoma.

ABSTRACT:

Backgrounds

Hepatocellular carcinoma (HCC) is characterized by an immunosuppressive tumor microenvironment (TME) that critically propels malignant evolution. Sphingomyelin synthase 2 (SGMS2), the pivotal sphingolipid metabolizing enzyme, catalyzes the conversion of ceramide to sphingomyelin. Emerging evidence highlights sphingolipid metabolism as a key regulator of tumor immunity, particularly in shaping macrophage phenotypes within the TME. However, the macrophage-specific contributions of SGMS2 to HCC progression remain unexplored. This study elucidates the critical role of SGMS2 in shaping TME and influencing patient prognosis.

Methods

Bulk RNA-seq analysis was performed using TCGA-LIHC datasets (n = 371). Single-cell RNA sequencing and spatial transcriptomics were used t

SUBMITTER: Meng F 

PROVIDER: S-EPMC12763894 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature