Nicotinamide mononucleotide enhances anti-tumor effect by resetting macrophages toward the inflammatory M1-like phenotype

Nicotinamide mononucleotide (NMN) supplementation has shown clinical benefits by regulating metabolic activities in the energy production process. Its protective effect and underlying immune regulatory mechanisms against tumor progression are still poorly understood. Here, we found that the high-dose NMN treatment could alter the level of several key NAD⁺ metabolic enzymes in human immune cells. Moreover, high-dose NMN treatment exhibited comparable antitumor efficacy as the PD-1 blockade in the murine mesothelioma challenge model. Subsequent immune profiling in both secondary lymphoid organ and tumor demonstrated that, rather than modulating T cell and NK cell responses, high-dose NMN treatment could reset tumor-associated macrophages toward the inflammatory M1-like phenotype compared with PD-1 blockade or non-treated subjects. These results provided a better understanding of NMN's regulatory effect on immune cells and suggested an alternative strategy of cancer immunotherapy.