Key Takeaways
- Metformin boosted CD8+ T cell activity in mice by increasing mitochondrial ROS and promoting immune cell growth.
- The anti-tumor effect wasn’t due to apoptosis, but to immune system modulation via interferon-γ secretion.
- Findings are preclinical — no human data yet, and the study didn’t test interactions with real-world cancer treatments.
A team of Okayama University scientists just helped shed light on an often proposed but poorly understood mechanism of metformin-dependent anticancer immunity. The study, published in the BMJ Journal for ImmunoTherapy of Cancer, reveals that the antidiabetic drug metformin, used in the treatment of type 2 diabetes, induces the activation and proliferation of tumor-targeted CD8+ T cells. These data raise awareness of the potential use of metformin as an anti-tumor immune support drug in patients with cancer.
Metformin
Cancer treatments have advanced significantly and, as with some viral infections, scientists hope that one day they will find a universal treatment that is effective against all the mutations and combinations of cancers that affect millions of people worldwide. Recent studies have shown that some drugs, such as the antidiabetic drug metformin, have anti-cancer properties. The use of metformin appears to enhance antitumor immunity. However, the underlying immunologic mechanisms are still poorly understood.
Metformin Stimulates CD8 Infiltrating T Cells
The Japanese team, therefore, studied how a specific subset of immune cells, called CD8+ infiltrating T cells (CD8TIL), which specifically attack cancer cells, behaves in response to metformin. The team conducted a series of experiments (in vitro) in tumor cell lines and (in vivo) in mice by genetically “inactivating” potential biomolecules that induce metformin-dependent anticancer immunity.
These experiments show that:
- Metformin induces the generation of reactive oxygen species in CD8TIL mitochondria and increases glycolysis.
- These reactive oxygen species (mtROS) activate growth pathways in CD8TIL, allowing the proliferation of these immune cells.
- This mechanism is promoted by a transcription factor involved in the antioxidant stress response, called Nrf.
- Metformin does not cause any anticancer effect through “cell suicide” or apoptosis.
- On the contrary, metformin induces strong secretion of interferon-ɣ by CD8TILs, which alters the tumor microenvironment in a way that promotes cancer cell death.
The lead author of the study, Professor Udono, hopes that understanding the mechanisms by which metformin, the antidiabetic drug, works will inspire new treatments. These data, the author concludes, already strongly suggest the possibility of using metformin as a drug to boost anti-cancer immunity in cancer patients.
Related Reading:
Mitochondrial Health Critical in Cancer, Diabetes, and Neurodegenerative Diseases
Autologous Bone Marrow Transplantation and Metformin, a Hope for the Cure of Multiple Sclerosis
Diabetes: Metformin Transfers Blood Sugar From the Blood to the Intestines
FAQs
Is metformin currently used to treat cancer?
No. It’s not approved for cancer treatment. The effects shown were in lab and animal models only.
Was this study done on humans?
No. The research was conducted in mice and tumor cell lines. Human impact is still untested.
Does metformin work for all cancer types?
That’s unknown. The study focused on specific immune responses and didn’t test across different cancers.
Can people take metformin to prevent cancer?
There’s no clinical evidence to support that. It should only be used for approved conditions like type 2 diabetes.
What about dosage — is it the same as in diabetic patients?
The study didn’t address dose equivalency in humans, so the real-world application is unclear.
Are there any side effects?
Yes. Common ones include nausea, diarrhea, and stomach discomfort. Rare but serious risks include lactic acidosis, especially in people with kidney problems.
Bottom Line
Yes, metformin showed it could activate CD8+ T cells in mice. But before anyone calls it a cancer breakthrough, let’s get real: this was a controlled lab setting, not a clinical trial. There’s no evidence yet that these immune effects translate to humans, let alone improve survival or outcomes in actual cancer patients.
The study didn’t explore how metformin interacts with standard cancer treatments. It didn’t compare effects across different tumor types or stages. And it didn’t address whether the dosages used in mice reflect anything meaningful for people already taking metformin for diabetes.
So while the mechanism of mitochondrial ROS and immune activation is scientifically interesting, we’ve seen plenty of “promising” preclinical results that never made it out of the lab. This could be one of them.
The takeaway? It’s a solid study, but don’t expect oncologists to start prescribing metformin for its immune perks anytime soon. If anything, it opens the door for more targeted research, not headlines.
References
Nishida, M., Yamashita, N., Ogawa, T., Koseki, K., Warabi, E., Ohue, T., Komatsu, M., Matsushita, H., Kakimi, K., Kawakami, E., Shiroguchi, K., & Udono, H. (2021). Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8⁺ T lymphocytes. Journal for ImmunoTherapy of Cancer, 9(9), e002954. https://doi.org/10.1136/jitc-2021-002954
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