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

Our plain-English summary of Nicotinamide mononucleotide enhances anti-tumor effect by resetting macrophages toward the inflammatory M1-like phenotype, by H. Xu, M.C.T. Wan, C.C.C. Wong, et al (Molecular Therapy. Oncology, 2026).

The study

• Authors: H. Xu, M.C.T. Wan, C.C.C. Wong, S. Qin, Y. Wen, J. Wang, Z. Chen
• Journal: Molecular Therapy. Oncology
• Published: 2026;34(2):201221
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© 2026 The Author(s).

In plain English

This brief report described laboratory experiments with cells and mice. It did not study asbestos exposure or people with mesothelioma. Researchers in Hong Kong tested nicotinamide mononucleotide (NMN), a compound involved in cell energy metabolism. First, immune cells from healthy blood donors were grown with human lung adenocarcinoma cells and given NMN at up to 10 mM. NMN raised levels of enzymes that make NAD+ (NMNAT 1 to 3) and lowered the enzyme NAMPT at the high dose. Next, mice (5 per group) were injected with a mouse mesothelioma cell line and given NMN, an anti-PD-1 antibody, or no treatment. The authors reported that high-dose NMN slowed tumor growth comparably to anti-PD-1. In the spleen, tumor-specific CD8+ T cells were significantly more frequent with anti-PD-1, but NMN did not have a similar effect. Instead, NMN shifted tumor macrophages toward an inflammatory 'M1-like' type and increased anti-tumor signaling molecules in macrophages. Removing macrophages significantly impaired NMN's tumor protection, and tumors then grew at a rate similar to untreated mice. The authors concluded that this macrophage shift might contribute to NMN's anti-mesothelioma effect, and they called their findings preliminary.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Brief report of laboratory experiments: human immune cells grown together with tumor cells in culture, and a tumor-challenge experiment in mice
• Who was studied: Male and female BALB/c mice from the University of Hong Kong, 5 per group, injected under the skin with AB1-Gag, a mouse mesothelioma cell line. The cell experiments used immune cells (PBMCs) from healthy Hong Kong Red Cross blood donors (median age 31), grown with the A549 human lung adenocarcinoma cell line.
• Exposure: No asbestos exposure was studied. The treatment studied was NMN. Mice received 300 mg/kg NMN by injection into the abdomen twice per week, compared with an anti-PD-1 antibody and with PBS (no treatment). In cell culture, NMN was given at 0, 1, 5 and 10 mM for 24 hours.
• Main results:
  • In human immune cells grown with tumor cells, NMN significantly increased the mRNA levels of NAD+ synthesis enzymes (NMNAT 1 to 3), and the increase was dose-dependent.
  • In the same human immune cells, the mRNA level of NAMPT decreased with high-dose (10 mM) NMN.
  • In mice with mesothelioma tumors, high-dose NMN inhibited tumor growth to a degree the authors described as comparable to PD-1 blockade. The text gives no numerical tumor sizes; those appear only in figures.
  • Tumor-specific CD8+ T cells in the spleen were significantly more frequent in the PD-1 blockade group. NMN did not have a similar effect.
  • Only in the NMN group did tumor macrophages change significantly: inflammatory M1-like macrophages increased and immunosuppressive M2-like macrophages decreased, compared with the other groups.
  • In NMN-treated mice, depleting macrophages with a CSF1R inhibitor significantly impaired NMN's tumor protection. Tumors then grew at a rate similar to untreated mice.
  • Mouse macrophages grown with tumor cells and NMN showed significantly higher mRNA levels of the anti-tumor cytokine TNF-alpha than untreated macrophages.
  • In tumors from NMN-treated mice, macrophages (but not T cells) showed consistent trends of protein-level changes in TNF-alpha, IL-12 beta and CD38. Macrophages also showed a higher frequency of IFN-gamma, with no difference in granzyme B.
• The authors' conclusion: The authors concluded that resetting tumor macrophages toward the M1-like type might contribute to the enhanced anti-mesothelioma effect of NMN treatment in mice. They described this as a possible alternative approach to immune checkpoint blockade.
• Limitations the authors state:
  • The authors stated that the detailed molecular mechanism still needs future investigation.
  • The authors described their findings as preliminary.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Mesothelioma, Immunotherapy.

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