Nicotinamide N-methyltransferase promotes M2 macrophage polarization by IL6 and MDSC conversion by GM-CSF in gallbladder carcinoma

• DOI: 10.1097/hep.0000000000000028
• Publication Date: 2023-01-12T13:01:09Z
• Authors: Yang Li; Bo Yang; Huijie Miao; Liguo Liu; Ziyi Wang; Chengkai Jiang; Yang Yang; Shimei Qiu; Xuechuan Li; Yajun Geng; Yijian Zhang; Yingbin Liu
• Keywords: Macrophage polarization

Background and Aims: Nicotinamide N-methyltransferase (NNMT), an enzyme responsible for the methylation of nicotinamide, is involved in many metabolic pathways adipose tissue liver. However, role NNMT editing tumor immune microenvironment not well understood. Approach Results: Here, we identified that can promote IL6 granulocyte-macrophage colony-stimulating factor (GM-CSF) expression by decreasing tri-methyl-histone H3 levels on promoters CSF2 (encoding GM-CSF) CCAAT/Enhancer Binding Protein, essential transcription expression, thus promoting differentiation macrophages into M2 type tumor-associated generation myeloid-derived suppressor cells from peripheral blood mononuclear cells. Treatment xenografted models overexpressing gallbladder carcinoma (GBC) with inhibitor JBSNF-000088 resulted compromised development decreased IL6, GM-CSF, macrophage marker CD206, cell CD33 but increased CD8. In addition, elevated tumors patients GBC was correlated CD206 CD8 survival patients. Conclusions: These data highlight critical progression. Inhibition a potential molecular target immunotherapy. Export