Skip to content
Free U.S. Standard shipping · Free international Standard shipping over US$150. Free U.S. shipping · International free over US$150.
Take the assessment

Explore HealthspanX

Preclinical mechanistic study

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

Haoran Xu, Marcus Chun Tao Wan, Chelsey Chi Ching Wong, Siqi Qin, Yang Wen, Jun Wang, Zhiwei Chen

Molecular Therapy Oncology · 2026 · 34(2):201221

Original publication PubMed Full text on PMC

Study at a glance

Design
Preclinical immunometabolism study combining human PBMC-tumor co-culture experiments with a BALB/c AB1-Gag murine mesothelioma challenge model and macrophage-depletion experiments.
Population or model
Healthy-donor human peripheral blood mononuclear cells in vitro and 8- to 10-week-old BALB/c mice with subcutaneous AB1-Gag mesothelioma tumors; no treated human cancer patients.
Sample size
Mouse treatment groups used approximately n=5 per group in the reported tumor-challenge and macrophage-depletion experiments; cell experiments used small replicate sets.
Intervention
High-dose NMN. In the mouse tumor model, NMN 300 mg/kg was administered intraperitoneally from tumor inoculation and twice weekly through day 14; comparator anti-PD-1 was 200 mg/kg. Human PBMC co-cultures used NMN concentrations up to 10 mM.
Publication type
Preclinical immunometabolism study
Evidence class
preclinical-mechanistic
Research area
Cancer immunometabolism
Trial registration
Not applicable (preclinical study)

Study endpoints

  • Tumor growth by size and luminescence
  • Tumor and splenic immune-cell composition
  • M1-like versus M2-like tumor-associated macrophage phenotype
  • Macrophage cytokine and activation markers
  • Effect of macrophage depletion on NMN-associated tumor control
  • NAD+ salvage-pathway enzyme expression in human PBMC co-cultures

Plain-language summary

This study investigated whether high-dose NMN could alter anti-tumor immune responses. The researchers first tested human immune cells in tumor-cell co-culture, then used a mouse mesothelioma model.

In mice, high-dose NMN slowed tumor growth to a degree reported as comparable with anti-PD-1 in this specific model. Unlike anti-PD-1, NMN did not mainly act through tumor-specific T cells. Instead, tumor-associated macrophages shifted toward an inflammatory M1-like phenotype, and depleting macrophages reduced the NMN-associated tumor-control effect.

The work is mechanistic and preclinical. It does not establish NMN as a cancer treatment, does not show benefit in human cancer patients, and does not establish safety alongside cancer therapy.

Key findings

  • NMN altered expression of NAD+ salvage-pathway enzymes in human PBMCs co-cultured with tumor cells.
  • In the AB1 mesothelioma mouse model, high-dose NMN reduced tumor progression relative to untreated controls.
  • NMN increased inflammatory M1-like tumor-associated macrophages and decreased M2-like macrophages.
  • Macrophage depletion substantially weakened the tumor-control effect seen with NMN, supporting macrophage involvement.
  • NMN increased macrophage activation/cytokine markers including TNF-α, IL-12β, CD38, and IFN-γ in reported experiments.
  • NMN did not reproduce the anti-PD-1-associated increase in tumor-specific CD8 T-cell responses.

Limitations

  • The anti-tumor findings were obtained in a mouse mesothelioma model, not in cancer patients.
  • The NMN regimen was a high-dose intraperitoneal experimental treatment and does not represent routine oral supplementation.
  • Group sizes were small and the study was a brief report rather than a clinical efficacy trial.
  • The model used an engineered AB1-Gag tumor system, which may not generalize to other cancers or human tumor microenvironments.
  • One author is an employee and shareholder of GeneHarbor, and the work included collaborative research support from GeneHarbor.
  • The study does not establish whether NMN could help, harm, or interact with standard cancer therapies in humans.

Funding and transparency

Funding

Zhiwei Chen reported support from the Theme-Based Research Scheme (T11-702/24-N) of the Hong Kong Research Grants Council, the University of Hong Kong Seed Fund for Translational and Applied Research, collaborative research with GeneHarbor (Hong Kong) Biotechnologies Limited, and University Development Fund and Li Ka Shing Faculty of Medicine Matching Fund support to the AIDS Institute.

Competing interests

Jun Wang is an employee and shareholder of GeneHarbor (Hong Kong) Biotechnologies.

HealthspanX observation

This paper is important because it shows that NMN can alter tumor immunobiology in a context-dependent way; it should not be converted into either a cancer-treatment claim or a blanket cancer-safety claim.

Interpretive weight

Mechanistic context

Human immune-cell co-culture and mouse mesothelioma experiments show a macrophage-linked antitumor mechanism, but this is preclinical cancer research and does not establish efficacy or safety in cancer patients.

This record summarizes a publication; it is not medical advice or a claim that a HealthspanX product reproduces the study's results. Report a correction.

Your cart (0)

Your cart is empty.

Explore Ultra Pure NMN, read the label and choose your pack when you’re ready.

Explore Ultra Pure NMNExplore the journal
HealthspanX

What are you looking for?

Useful starting points