Dietary vitamin B3 supplementation induces the antitumor immunity against liver cancer via biased GPR109A signaling in myeloid cell

Yang Yang; Tianduo Pei; Xiaolin Hu; Yu Lu; Yanqiu Huang; Tingya Wan; Chaobao Liu; Fengqian Chen; Bao Guo; Yuemei Hong; Qian Ba; Xiaoguang Li; Hui Wang

doi:10.1016/j.xcrm.2024.101718

Dietary vitamin B3 supplementation induces the antitumor immunity against liver cancer via biased GPR109A signaling in myeloid cell

Cell Rep Med. 2024 Sep 17;5(9):101718. doi: 10.1016/j.xcrm.2024.101718.

Authors

Yang Yang¹, Tianduo Pei¹, Xiaolin Hu¹, Yu Lu¹, Yanqiu Huang¹, Tingya Wan¹, Chaobao Liu¹, Fengqian Chen¹, Bao Guo¹, Yuemei Hong¹, Qian Ba², Xiaoguang Li³, Hui Wang⁴

Affiliations

¹ State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
² State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: [email protected].
³ State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: [email protected].
⁴ State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: [email protected].

Abstract

The impact of dietary nutrients on tumor immunity remains an area of ongoing investigation, particularly regarding the specific role of vitamins and their mechanism. Here, we demonstrate that vitamin B3 (VB3) induces antitumor immunity against liver cancer through biased GPR109A axis in myeloid cell. Nutritional epidemiology studies suggest that higher VB3 intake reduces liver cancer risk. VB3 supplementation demonstrates antitumor efficacy in multiple mouse models through alleviating the immunosuppressive tumor microenvironment (TME) mediated by tumor-infiltrating myeloid cell, thereby augmenting effectiveness of immunotherapy or targeted therapy in a CD8⁺ T cell-dependent manner. Mechanically, the TME induces aberrant GPR109A/nuclear factor κB (NF-κB) activation in myeloid cell to shape the immunosuppressive TME. In contrast, VB3 activates β-Arrestin-mediated GPR109A degradation and NF-κB inhibition to suppress the immunosuppressive polarization of myeloid cell, thereby activating the cytotoxic function of CD8⁺ T cell. Overall, these results expand the understanding of how vitamins regulate the TME, suggesting that dietary VB3 supplementation is an adjunctive treatment for liver cancer.

MeSH terms

Animals
CD8-Positive T-Lymphocytes* / drug effects
CD8-Positive T-Lymphocytes* / immunology
CD8-Positive T-Lymphocytes* / metabolism
Cell Line, Tumor
Dietary Supplements*
Humans
Liver Neoplasms* / drug therapy
Liver Neoplasms* / immunology
Liver Neoplasms* / metabolism
Liver Neoplasms* / pathology
Male
Mice
Mice, Inbred C57BL
Myeloid Cells* / drug effects
Myeloid Cells* / immunology
Myeloid Cells* / metabolism
NF-kappa B* / metabolism
Receptors, G-Protein-Coupled* / metabolism
Receptors, Nicotinic* / metabolism
Signal Transduction* / drug effects
Tumor Microenvironment* / drug effects
Tumor Microenvironment* / immunology

Substances

Receptors, G-Protein-Coupled
NF-kappa B
Receptors, Nicotinic
Hcar2 protein, mouse
HCAR2 protein, human