Nuclear OXCT1 attenuates histone β-hydroxybutyrylation-mediated MHC-I transcription.

Nuclear OXCT1 reduces histone β-hydroxybutyrylation at MHC-I loci, decreasing immune gene transcription and impacting hepatocellular carcinoma response to immunotherapy.

• Why it matters: Understanding metabolic factors that influence immunotherapy effectiveness is crucial for improving treatment outcomes, especially in cancers like HCC where responses vary.
• What they did: The study used multiomics analysis of HCC tumor biopsies and identified that increased OXCT1 expression correlates with poor ICB response, while its substrate BHB has the opposite effect.
• The result: Targeting the AMPK-OXCT1-IRF1 pathway enhances tumor sensitivity to ICB, revealing a link between ketone metabolism and immune gene regulation that could inform new therapeutic strategies.