Intestinal bacteria reinforce chemotherapy

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The intestinal flora stimulates an person's immune responses to combat cancer during chemotherapy, according to newly published research. The efficacy of cyclophosphamide, a commonly used chemotherapy agent, relies to an extent on its capacity to mobilize certain bacteria from the intestinal flora toward the bloodstream and lymph nodes.

Cyclophosphamide is one of the most widely used drugs in chemotherapy. However, like any treatment, it involves side effects, such as inflammation of the mucosa, and disrupts the normal balance of the intestinal microbiota. Certain Gram-positive bacteria can pass the intestinal barrier and enter the bloodstream and lymph nodes.

Once inside the lymph nodes, these bacteria stimulate fresh immune defenses that then enhance the body's ability to fight the malignant tumor. These bacteria, once in the general circulation of the body, may be considered harmful, and the body generates an immune response.

“This chain reaction, a side effect of the treatment, actually turns out to be very useful,” explained corresponding author Laurence Zitvogel, PhD, of Institut Gustave Roussy in Villejuif, France. “Surprisingly, the immune response directed against these bacteria helps the patient to better fight his/her tumor, by stimulating fresh immune defense mechanisms.”

More specifically, immunization against bacteria leads to the recruitment of effector lymphocytes different from those mobilized by chemotherapy. These effector lymphocytes help antitumor lymphocytes to stem the growth of tumors.

These results were examined in tumor-bearing mice that were germ-free or had been treated with antibiotics to kill Gram-positive bacteria; the tumors of these mice were resistant to cyclophosphamide. When these mice received a transfer of the pathogenic T-helper cells, the cyclophosphamide had some of its efficacy restored.

The researchers also suggested that some antibiotics used during chemotherapy may destroy these Gram-positive bacteria, and thus negate their beneficial effect. This study was published in Science (2013; doi:10.1126/science.1240537).

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