The researchers found two species of gut bacteria that boost the antitumor effect of chemotherapy by activating a type of immune cell that attacks cancer.
The researchers, including co-senior author Dr. Mathias Chamaillard, research director of the Center for Infection and Immunity of Lille (Inserm/CNRS/Lille University/Institut Pasteur de Lille) in France, report their findings in the journal Immunity.
The study concerns the complex interplay in the human body of three things in fighting cancer: chemotherapy, the immune system, and gut bacteria.
Chemotherapy can be used to cure cancer, reduce the chances it will return, or stop or slow its growth. It can also be used to shrink tumors that are causing pain and other problems.
The immune system also has mechanisms for fighting cancer. For instance, it has T cells that hunt down and kill cancer cells.
As technologies in microbiology and molecular biology advance, scientists are finding that the trillions of microbes that live in and on our bodies play an important role in health and disease.
In the intestines, for example, gut bacteria not only help to digest food, their byproducts (metabolites) also improve immune function and strengthen the lining of the gut to better defend against infection.
Two gut bacteria boost the effect of cyclophosphamide
In the new study, Dr. Chamaillard and colleagues show that two species of gut bacteria - Enterococcus hirae and Barnesiella intestinihominis - boost the effect of the commonly prescribed immunosuppressive chemotherapy drug cyclophosphamide by activating T cells.
- Chemotherapy often accompanies other cancer treatments
- For example, it may be used to make a tumor smaller before surgery or radiation therapy
- The most common side effect is fatigue.
Moreover, they showed that the immune response boosted by these bacteria predicted longer progression-free survival in patients with advanced lung and ovarian cancers who were treated with chemo-immunotherapy.
Dr. Chamaillard says the finding shows it may be possible to improve the design of anticancer treatments, by "either optimizing the use of antibiotics, or implementing supplementation with so-called oncomicrobiotics or their bioactive metabolites, to promote the efficacy of anticancer drugs."
As a first step, the team used mouse models to investigate the effects of the two bacteria species separately with chemotherapy.
They found oral treatment with E. hirae activated antitumor T cell responses in the spleen, which, alongside toxic effects of the chemotherapy drug cisplatin, curbed tumor growth.
They also found similar results from oral treatment with B. intestinihominis - except in that case, the bacteria spurred T cells to infiltrate tumors in various mouse models.
Predicted progression-free survival
Moving on from mouse models, the team then analyzed blood T cell responses from 38 patients with advanced lung and ovarian cancer who were treated with chemo-immunotherapy.
The results showed memory T cell responses specific to E. hirae and B. intestinihominis predicted progression-free survival - that is, the amount of time after treatment that patients live with the disease without it getting worse.
The researchers are now planning further studies to find out which specific bacterial metabolites or immune-modulating molecules are responsible for boosting the effect of cyclophosphamide.
"Answering this question may provide a way to improve the survival of cyclophosphamide-treated cancer patients by supplementing them with bacterial-derived drugs instead of live microorganisms."
Dr. Mathias Chamaillard