Recent studies have shown that certain gut microbes encourage tumours to grow, whereas others contribute to making cancer treatments more effective. It remained necessary to identify the nature and mode of action of the bacterial species capable of optimising the antitumour response induced by chemotherapy.
In this new study, Mathias Chamaillard, Laurence Zitvogel and their collaborators showed that two gut bacteria, Enterococcus hirae and Barnesiella intestinihominis, together potentiate the therapeutic effects of cyclophosphamide, a chemotherapeutic agent used to treat many cancers.
How? Chemotherapy has secondary effects that include increased permeability of the intestinal barrier and, consequently, the entry of the bacteria constituting the microbiota into the bloodstream. To combat this abnormal entry of bacteria into the bloodstream, an immune response is initiated. Against all expectations, this response is beneficial for patients, since it can also lead to the destruction of the tumour cells. The tumour is therefore attacked directly by cyclophosphamide and indirectly by this “booster” effect of the bacteria.
Several preclinical models enabled the researchers to demonstrate that the antitumour immune response induced by cyclophosphamide is optimised after oral administration of E. hirae. Treatment by oral administration of B. intestinihominis enabled a similar effect to be obtained.
The researchers then analysed the immune profile of the blood lymphocytes from 38 patients with advanced stage cancer of the lung or ovary, and treated by chemoimmunotherapy. They discovered that the presence of T memory lymphocytes specific for E. hirae and B. intestinihominis makes it possible to predict the period for which a patient lives with a cancer without it getting worse, during and after a treatment.
“The efficacy of a cancer drug relies on a complex interaction between the patient’s microbiome and his/her ability to mount an effective immune response against certain bacteria of the gut microbiota,” explains one of the main authors of the study, Mathias Chamaillard, Inserm Research Director.“These results allow us to consider increasing the efficacy of these treatments by optimising the use of antibiotics, but also by supplementing the numbers of certain bacteria, known as oncobiotics (or their active substances), which are able to enhance the effect of cancer drugs.”
The researchers have planned to identify, in future studies, the specific parts of the bacteria responsible for enhancing the effects of cyclophosphamide. “If we succeed in answering this question, we can perhaps find a way of improving the survival of the patients treated using this chemotherapy by giving them drugs derived from these bacteria,” concludes Mathias Chamaillard.
 Unit 1019, “Center for Infection and Immunity of Lille” (Inserm/CNRS/University of Lille/Institut Pasteur Lille)
 Unit 1015, “Immunology of Tumours and Immunotherapy” (Inserm/Gustave Roussy Institute/Paris-Sud University)
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