In the fight against cancer, modern medicine has made gradual progress. With so many different types of cancer affecting millions of people throughout the world, a broad but focused treatment would be ideal.
Certain medications, such as metformin which is used to treat lifestyle disorders, including type 2 diabetes, have recently been discovered to have anti-cancer properties. Metformin treatment appears to boost antitumor immunity. However, scientists have yet to discover the underlying immunological pathways.
An Antitumor Immune Response That Requires Metformin
Among the medical fraternity, the importance of this chemical composition and content is much known for its effects on blood sugar. However, with the help of the same element now, it is possible to derive other benefits also. In a study, it is revealed that metformin can also help one get better immunity against the tumors, which may otherwise lead to a threat to life also.
When the study’s leader Prof. Udono lost his father to cancer, he almost gave up on his anti-cancer efforts. However, he claims that inspiration came knocking at a conference: “Nearly ten years ago, a switch turned on in my head when I attended a Keystone Symposia discussing cancer and hypoxia held in Banff.
Alberta. I realized that we had missed addressing the Warburg effect, an effect that bolsters the growth of cancer in our previous research. So, reverting the Warburg effect to a normal metabolic profile in cancers became a topic that got me thinking. Surprisingly I got a hint from the same conference that metformin may aid cancer immunity. So we got to work.”
Professor HeiichiroUdono and his team of Japanese scientists decided to tackle this oncological research challenge. They investigated how a subset of immune cells known as CD8+ infiltrating T-lymphocytes (CD8TIL), which selectively assault tumor cells, reacted to metformin in a recent study. Their findings were reported in the Journal of Cancer Immunotherapy.
Prof. Udono and his colleagues methodically carried out a series of tests on cancer cell lines and a knock-out mice model to identify potential macromolecules that cause metformin-dependent antitumor immunity.
They investigated the intracellular pathways in CD8TIL when exposed to metformin as well as other indicators for growth to arrive at their conclusions. They also looked at the quantities of interferons produced by CD8TIL, which are used to target cancer cells.
Prof. Udono, when speaking about the findings, exclaims, “Above all, our research demonstrates that we can defend our bodies from cancer by ourselves.
We hope that by gaining a better understanding of cancer, we will be able to not only reduce cancer incidence and enhance therapy but also help people live longer.” These data also clearly imply that metformin could be used to boost antitumor immunity in cancer patients, according to the researchers.
Metformin induces the production of reactive oxygen species (mtROS) in CD8TIL mitochondria and enhances glycolysis, according to the researchers. They also discovered that mtROS activated CD8TIL growth pathways allowing these immune cells to proliferate. This is accomplished in part by the transcription factor Nrf which is implicated in the anti-oxidative stress response.
In conclusion, we found that metformin administration stimulated NK cells in vitro and in vivo resulting in increased antitumor immunity. In addition, we found that metformin enhanced innate immunity in NK cells in part via activating the JAK1/2/3/STAT5 and AKT/mTOR pathways in a p38 MAPK-dependent manner. Our findings back up the theory that metformin boosts antitumor immunity in the body and helps checkpoint cancer immunotherapies work more effectively.
However, these findings will require further examination in future clinical investigations to be confirmed. Our findings may also open up new avenues for understanding metformin’s powerful antitumor immunity action.
