Hepatic TM6SF2 activates antitumour immunity to suppress metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma and boosts immunotherapy.

ABSTRACT:

Background

Transmembrane 6 superfamily member 2 (TM6SF2) has a protective role against metabolic dysfunction-associated steatotic liver disease (MASLD).

Objective

We aim to investigate the mechanistic role and therapeutic potential of hepatic TM6SF2 in MASLD-related hepatocellular carcinoma (HCC).

Design

Hepatocyte-specific Tm6sf2 knockout (Tm6sf2 ^∆hep) mice were fed with high-fat/high-cholesterol (HFHC) diet or diethylnitrosamine plus HFHC diet to induce MASLD-HCC. TM6SF2 function was also evaluated in orthotopic MASLD-HCC mice. Human MASLD-HCC specimens were included to evaluate clinical significance.

Results

TM6SF2 was downregulated in tumours compared with adjacent normal tissues from MASLD-HCC patients. Hepatocyte-specific Tm6sf

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12014897 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature