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

Autor:	Yang Y; 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., Pei T; 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., Hu X; 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., Lu Y; 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., Huang Y; 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., Wan T; 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., Liu C; 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., Chen F; 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., Guo B; 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., Hong Y; 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., Ba Q; 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: qba@shsmu.edu.cn., Li X; 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: lixg@shsmu.edu.cn., Wang H; 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: huiwang@shsmu.edu.cn.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Sep 17; Vol. 5 (9), pp. 101718.
DOI:	10.1016/j.xcrm.2024.101718
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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