Antibiotics May Reduce Chemotherapy’s Effectiveness, Study Suggests

Antibiotics May Reduce Chemotherapy’s Effectiveness, Study Suggests
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Using antibiotics in cancer patients may significantly reduce the effectiveness of chemotherapy agents, which appear to require help from the body’s immune system to function, according to a study by researchers at Augusta University in Georgia.

The research, “The impact of antibiotic usage on the efficacy of chemoimmunotherapy is contingent on the source of tumor-reactive T cells,” was published in the journal Oncotarget.

Antibiotics are prescribed to prevent and treat infections frequently caused by chemotherapy. However, increasing evidence shows that they may significantly hamper cancer treatment.

“It likely depends on what types of therapy physicians are giving to patients and how often they also are giving them antibiotics,” Gang Zhou, an immunologist at the Georgia Cancer Center and the study’s senior author, said in a press release.

Antibiotics impact treatment through their effects in the gut, where the vast number of microbes that form the microbiota activate immune cells to initiate the body’s response to cancer, Zhou said.

But the study shows that antibiotics may reduce the effectiveness of cancer therapies requiring T-cells, which are key immune cells in the fight against tumors.

Specifically, investigators found that antibodies have a mixed effect on an immunotherapy called adoptive T-cell therapy, which consists of altering a patient’s T-cells to improve their anti-cancer properties.

However, one of these therapies, CAR T-cell therapy, is not affected by antibiotics, even after long-term use in an animal model of lymphoma. This likely is because the therapy is not highly dependent on the body’s innate immune system.

In CAR T-cell therapy, a patient’s own T-cells are engineered to contain a tumor-finding receptor called CAR, to increase the cells’ anti-cancer efficacy. The therapy, which is usually given to patients who failed several other treatments, requires chemotherapy to deplete part of the patient’s T-cells.

In contrast, a different type of adoptive T-cell therapy was impacted by antibiotics. In this approach, researchers transferred a subtype of T-cells called tumor-specific CD4+ T-cells to treat a mouse model of colorectal cancer.

Unlike CAR T-cell therapy, tumor-specific CD4+ T-cells still require help from the innate immune system to fight the cancer cells, Zhou said.

In these mice, antibiotics impaired the effectiveness of treatment with chemotherapy and CD4+ T-cells in three out of five mice.

Using antibiotics also impacted the efficacy of the widely used chemotherapy medication cyclophosphamide when used alone to treat B-cell lymphoma. Cyclophosphamide needs support from the body’s T-cells, which are disrupted by antibiotics.

“These findings may have implications for the judicial use of antibiotics in cancer patients receiving chemoimmunotherapies,” the investigators wrote.

Similar preclinical findings had been reported in studies of sarcoma, where the altered gut microbiota impacts chemotherapy’s effectiveness.

“There is also emerging clinical evidence showing that for cyclophosphamide-based chemotherapy, some patients who also get antibiotics for a longer period of time, seem to have less optimal outcomes,” Zhou said.

Further research in humans is needed to provide more information on how to manage antibiotics use in patients being treated for cancer, Zhou added.

In addition to the anti-cancer response, researchers further demonstrated that continued treatment with antibiotics also suppressed the immune response.

Chemotherapy may limit the success of immunotherapy, even in the absence of antibiotics. Establishing the optimal combination of these treatments is a current focus of scientists and clinicians.

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