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.
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.
Cell Rep Med. 2024 Sep 17;5(9):101718. doi: 10.1016/j.xcrm.2024.101718.
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.
膳食营养素对肿瘤免疫的影响仍然是一个正在进行的研究领域，特别是关于维生素的具体作用及其机制。在这里，我们证明维生素 B3（VB3）通过髓系细胞中偏向性 GPR109A 轴诱导肝癌抗肿瘤免疫。营养流行病学研究表明，较高的 VB3 摄入量可降低肝癌风险。VB3 补充通过减轻肿瘤浸润性髓系细胞介导的免疫抑制肿瘤微环境（TME），从而以 CD8 T 细胞依赖的方式增强免疫疗法或靶向治疗的效果，在多种小鼠模型中显示出抗肿瘤功效。从机制上讲，TME 在髓系细胞中诱导异常的 GPR109A/核因子 κB（NF-κB）激活，以塑造免疫抑制性 TME。相比之下，VB3 激活β-抑制蛋白介导的 GPR109A 降解和 NF-κB 抑制，以抑制髓系细胞的免疫抑制极化，从而激活 CD8 T 细胞的细胞毒性功能。总的来说，这些结果扩展了我们对维生素如何调节 TME 的理解，表明膳食 VB3 补充是肝癌的辅助治疗方法。
