Anti-Tumour Immunity Relies on Targeting Tissue Homeostasis Through Monocyte-Driven Responses Rather Than Direct Tumour Cytotoxicity.

ABSTRACT:

Background

Metabolic dysfunction-associated fatty liver disease (MAFLD) can progress to hepatocellular carcinoma (HCC), yet the immune mechanisms driving this transition remain unclear.

Methods

In a chronic Western diet (WD) mouse model, we performed single-nuclei RNA sequencing to track MAFLD progression into HCC and subsequent tumour inhibition upon dietary correction.

Results

Carcinogenesis begins during MAFLD, with tumour cells entering dormancy when HCC is mitigated. Rather than purely tolerogenic, the liver actively engages immune responses targeting myofibroblasts, fibroblasts and hepatocytes to maintain tissue homeostasis. Cytotoxic cells contribute to the turnover of liver cells but do not primarily target the tumour. NKT cells predominate under chronic WD, w

SUBMITTER: Koelsch N 

PROVIDER: S-EPMC12020664 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature