The chemotherapy drug cyclophosphamide is recognized for its ability to stimulate anti-tumor responses in the immune system. Now, a new study recently published in Science suggests it gets help from gut bacteria to do this.
There are more than 100,000 billion bacteria in the gut - which collectively behave like an organ. They are crucial to our health. Not only do they help to digest and break down food into essential nutrients to be absorbed and metabolized in the body, they also eliminate potentially toxic substances and defend against pathogens.
This microbe community or "microbiome" is with us from birth and plays a key role in the maturation of the immune system.
But the mix of microbe species in the gut varies from person to person, to the extent that the presence or absence of one or more species appears to have an effect on whether we develop certain diseases, or are able to withstand them.
And this appears also to be true of diseases like cancer, as suggested by this latest study, the results of which surprised the French researchers, from the Institut Gustave Roussy, Inserm, Institut Pasteur and from INRA (French National Agronomic Research Institute), who made the discovery.
Drug stimulates gut bacteria to trigger immune defences
They found that cyclophosphamide's effect depends on its ability to stimulate certain gut bacteria to move into the bloodstream and lymph nodes, where they trigger new immune defenses that boost the body's ability to fight the malignant tumor.
Cyclophosphamide is one of the most widely used drugs in chemotherapy, but it has side effects. One of these is to disrupt the normal balance of gut microbe species. Some of the bacteria (the Gram positive type) can breach the intestinal barrier and get into the bloodstream and lymph nodes.
The immune system responds to this breach by mounting a defence against any potential harm the bacteria may cause.
Prof. Laurence Zitvogel, a medical oncologist at the Institut Gustave Roussy, and also a research director at Inserm, says such a "chain reaction" side effect of treatment could actually be useful:
"Surprisingly, the immune response directed against these bacteria helps the patient to better fight his/her tumor, by stimulating fresh immune defence mechanisms."
More specifically, she explains, the immune reaction against the bacteria summons effector lymphocytes - a group of white blood cells - that are different to those mobilized by the chemo drug. These new recruits help anti-tumor immune cells to stem tumor growth.
The team tested this idea by treating mice with no Gram positive bacteria in their gut with the chemotherapy drug and showed its effect was reduced.
They also proposed that taking antibiotics during chemotherapy could reduce its effects by destroying the Gram positive bacteria.
They suggest now that we know which gut bacteria boost the anti-tumor immune response, the next step should be to see how to increase them in the gut, perhaps using pro- or pre-biotics or through specific dietary changes.
Funds from the French National Cancer League, the French National Cancer Institute and LABEX Onco-Immunology helped finance the study.
In 2011, researchers from Purdue University in the US reported successfully boosting anti-cancer therapy with tiny oxygen generators implanted in tumors.