Tier 3 — preclinical

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

Bibliography

PubMed
PMID 42179971
PubMed Central
PMC13195322
DOI
10.1016/j.omton.2026.201221
Funding
Supported by Hong Kong Research Grants Council, University of Hong Kong translational and development funds, Li Ka Shing Faculty of Medicine matching funds, and collaborative research with GeneHarbor (Hong Kong) Biotechnologies Limited.
Competing interests
Jun Wang was an employee and shareholder of GeneHarbor (Hong Kong) Biotechnologies Limited.

Study snapshot

DesignHuman immune-cell mechanistic experiments plus controlled murine mesothelioma tumor-challenge and immune-profiling experiments.
ModelHuman immune cells in vitro and BALB/c mice challenged with mesothelioma tumor cells.
SampleMultiple immune-cell and mouse experiments; no cancer patients received NMN.
InterventionHigh-dose NMN treatment compared with untreated controls and, in selected mouse experiments, PD-1 blockade.
DurationVaried by immune-cell and tumor-challenge experiment.
EndpointsTumor growth; NAD+ salvage enzymes; Tumor-associated macrophages; M1-like macrophage phenotype; T-cell responses; NK-cell responses; Cytokines

What the study showed, in plain terms

This 2026 preclinical study points in the opposite direction from some cancer-safety experiments: high-dose NMN suppressed tumor progression in a mouse mesothelioma model.

The proposed mechanism was not direct tumor-cell toxicity. NMN shifted tumor-associated macrophages toward a more inflammatory M1-like phenotype, while T-cell and NK-cell responses were not the main apparent drivers.

Together with studies showing possible tumor protection in other models, this reinforces that NAD+ manipulation in cancer is context-dependent. It does not support using NMN as a cancer treatment.

Key findings

  • High-dose NMN changed expression of NAD+ metabolic enzymes in immune cells.
  • In the murine mesothelioma model, high-dose NMN produced antitumor activity comparable to PD-1 blockade under the study conditions.
  • Immune profiling linked the effect primarily to a shift in tumor-associated macrophages toward an inflammatory M1-like phenotype.
  • T-cell and NK-cell responses did not appear to explain the main effect.
  • The study provides mechanistic cancer-immunology evidence, not clinical treatment evidence.

What this study can and cannot tell us

The antitumor efficacy was demonstrated in a mouse mesothelioma model, not in people. High-dose experimental exposure should not be extrapolated to routine supplement use.

One co-author was an employee and shareholder of a biotechnology company involved in collaborative research funding. Independent replication and human trials would be required before clinical conclusions.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology