Histone lactylation-driven feedback loop modulates cholesterol-linked immunosuppression in pancreatic cancer.

ABSTRACT:

Background

Pancreatic cancer exhibits limited clinical responses to immunotherapy, highlighting the need for new strategies to counteract its immunosuppressive microenvironment. Although metabolic reprogramming and epigenetic changes contribute to malignancy, the impact of lactate-driven histone lactylation on the tumour microenvironment (TME) has not been fully explored.

Objective

This study aims to investigate the role of histone lactylation in pancreatic cancer, focusing on its effects on cholesterol metabolism and antitumour immunity.

Designs

Global lactylome profiling was conducted to identify novel epigenetic mechanisms driven by lactate-induced histone lactylation. Mechanisms were investigated via RNA sequencing, CUT&Tag, immunoprecipitation-mass spectrometry a

SUBMITTER: Yang J 

PROVIDER: S-EPMC12573332 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature