Highlights: 

  • NMN enhances the effect of natural killer (NK) cells — immune cells that kill cancer cells — to increase the lifespan of mice with cancer by nearly 3-fold. 
  • NK cell tumor suppression is amplified by NMN in liver cancer mouse model. 
  • Tumor growth is also reduced by NMN-treated NK cells in skin cancer mouse model.

The true assassins of our immune system, NK cells, are capable of destroying virus-infected and cancer cells directly. However, to kill off the bad cells, NK cells require lots of energy. Without enough energy, NK cells can become impaired, leading to unchecked tumor growth. Now, researchers at Shandong University may have found a way to restore this energy. 

As reported in Hepatology, nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) invigorates the anti-tumor capabilities of NK cells. Guo and colleagues show that NMN-treated NK cells increase the lifespan of mice modeling liver cancer (hepatocellular carcinoma) by nearly 3-fold while reducing tumor growth. Furthermore, they show that NMN decreases tumor size in mice modeling skin cancer (melanoma). 

NMN Puts Cancer Killing Cells into Overdrive

To model liver cancer in mice, Guo and colleagues injected extremely immunodeficient mice with liver cancer cells to induce tumor growth. To give NK cells a boost of energy and experiment with NK cell-based cancer therapy, the China-based researchers supplemented NK cells with NMN. By injecting the cancerous mice with NMN-treated NK cells, the researchers saw significant improvements in the overall survival of the tumor-bearing mice.

(Guo et al., 2022 | Hepatology) NMN-Treated NK Cells Increase Lifespan. Immunodeficient mice injected with liver cancer cells (black) live longer when injected with NK cells (red) and live even longer when the NK cells are treated with NMN (blue).

NAD+ is an essential molecule that mediates the production of cellular energy (ATP). By treating NK cells with NMN, NAD+ levels are increased, allowing for the production of more cellular energy. Armed with sufficient fuel, NK cells can more efficiently kill tumor cells and suppress tumor growth. 

(Guo et al., 2022 | Hepatology) NMN-Treated NK Cells Suppress Liver Tumor Growth. Immunodeficient mice injected with liver cancer cells (control) have less tumor growth (measured by fluorescing tumors) when injected with NK cells (mock NK-92), and even less tumor growth when the NK cells are treated with NMN (NMN-treated NK-92).

In another cancer model, Guo and colleagues injected skin cancer cells underneath the skin of mice. These mice were then injected with NMN-treated NK cells, their tumors were subsequently harvested for measurement. It was found that NMN-treated NK cells reduce tumor size more effectively than untreated NK cells. Taken together, these findings suggest that, compared to untreated NK cells, NMN-treated NK cells can more efficiently suppress tumor growth for multiple types of cancer.

(Guo et al., 2022 | Hepatology) NMN-Treated NK Cells Suppress Skin Tumor Growth. Mice modeling skin cancer have smaller tumors when injected with NMN-treated NK cells compared to untreated NK cells (mock NK).

Is NMN Key in Immune Cell Cancer Therapy?

Immunotherapy — stimulating the immune system to fight cancer — is an emerging alternative to chemotherapy — using chemicals to fight cancer. Furthermore, NK cells are on the frontier of immunotherapeutic options, owing to their safety profile. However, in the body, NK cell efficiency is hindered by factors surrounding the tumor environment (tumor microenvironment). The findings of Guo and colleagues suggest that NMN can mitigate this hindrance. Additionally, a previous study showed that NMN enhances NK cell efficiency as well, supporting this idea. Thus, treating NK cells with NMN may solve many of the efficiency problems associated with NK cell immunotherapy.

In addition to destroying virus-infected and cancer cells, NK cells have been shown to destroy senescent cells, an effect that is enhanced by the neurotransmitter dopamine. Senescent cells are cells that can no longer divide but secrete pro-inflammatory molecules that can damage tissue. Senescent cells accumulate with aging and the inflammation they cause is thought to underly many age-related diseases. Therefore, NK cells could potentially be used to slow aging by targeting senescent cells, an effect that could apparently be enhanced by NMN (and dopamine).