Study Shows Metformin Maximizes Immune Memory
By Daniel J. DeNoon
WebMD Health News
Reviewed by Louise Chang, MD
"These findings were unanticipated, but are potentially extremely important and could revolutionize current strategies for both therapeutic and [preventive] vaccines," University of Pennsylvania researcher Yongwon Choi, PhD, says in a news release.
Choi's team wasn't initially interested in diabetes drugs -- and wasn't trying to improve immunizations.
This so-called immune memory depends on cells called memory T cells that lurk in the body, becoming active only in the presence of the pathogen they're programmed to recognize.
During an infection -- or after an immunization -- the body mounts a massive T-cell response to fight off the invasion. These T cells go away after the threat is neutralized, but a few of them survive to become memory T cells. How this happens has been a mystery.
Choi's team found that memory T cells survive by switching their fuel supply. Instead of burning glucose, as most cells do, they start burning fat. The researchers bred a strain of mice that lacked the ability to switch fuel sources, and these mice could no longer make memory T cells.
One of metformin's effects is to help cells burn fat. When Choi and colleagues gave metformin to the specially bred mice, the drug restored the animals' ability to make memory T cells.
This led the researchers to wonder what would happen if they gave metformin to normal mice. So they injected the mice with doses of an experimental cancer vaccine that, under normal circumstances, does not protect the animals. But in mice given metformin, the vaccine was vastly more effective at preventing cancer.
"The finding was very unexpected. We were lucky," Choi tells WebMD.
The serendipity may pay off in big ways.
"The findings do not mean that if you take metformin you automatically have better memory responses," Choi says. "But this widely used drug might enhance vaccination programs. If we combine our finding with those strategies, we may be able to improve vaccine efficacy."
Choi and colleagues report their findings in today's advance online issue of Nature.
Pearce, E.L. Nature, advance online publication, June 4, 2009.
Yongwon Choi, PhD, professor of pathology and laboratory medicine, University of Pennsylvania, Philadelphia.
News release, University of Pennsylvania.
News release, McGill University.
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