Evidence have emerged that frequent use of antibiotics leave us drug resistant and vulnerable to infection and now new study has revealed that antibiotics could negatively impact cancer treatment efficacy.
Scientists have urged that during increasingly complex, targeted treatment of cancer, judicious use of antibiotics is to be done to ensure that instead of fighting infections they don’t end up having unintended consequence of also hampering cancer treatment.
Any negative impact of antibiotics on cancer treatment appears to go back to the gut and to whether the microbiota is needed to help activate the T cells driving treatment response, says Dr. Gang Zhou, immunologist at the Georgia Cancer Center and the Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Augusta University.
They have some of the first evidence that in some of the newest therapies, the effect of antibiotics is definitely mixed. Infections are typically the biggest complication of chemotherapy, and antibiotics are commonly prescribed to prevent and treat them.
In this high-stakes arena, where chemotherapy is increasingly packaged with newer immunotherapies, Bryan, Zhou and their colleagues have more evidence that antibiotics’ impact on the microbiota can mean that T cells, key players of the immune response, are less effective and some therapies might be too.
They report that antibiotic use appears to have a mixed impact on an emerging immunotherapy called adoptive T-cell therapy, in which a patient’s T cells are altered in a variety of ways to better fight cancer.
They found that one of the newest of these – CAR T-cell therapy – is not affected by antibiotics, likely because it is not so reliant on the innate immune system.
Even long-term antibiotic use does not seem to hinder the efficacy of CAR T-cell therapy against systemic lymphoma in their animal model. While they could see the impact of antibiotics on the microbiota, mice with CAR T-cell therapy continued to respond well to cancer treatment.
But the efficacy of another mode of adoptive T-cell therapy was impacted. This model mimics therapy in which receptors that target the patient’s tumor are put onto their T cells. In this case, the researchers transferred tumor-specific CD4+T cells to treat mice with colorectal cancer.
One key difference here is that, unlike the CAR T-cell therapy, these engineered T cells still need help from the innate immune system to fight the tumor, now that they can better target it, Zhou says.
Mice with colorectal cancers that did not receive antibiotics were cured after being treated with the chemotherapy CTX followed by CD4+T-cell therapy. However, with antibiotics on board, this curative effect was lost in three out of five mice three weeks after treatment.
Their studies also confirmed that antibiotic use impacts the efficacy of the widely used CTX, when it’s used alone, in this case to treat B-cell lymphoma. In addition to directly killing rapidly dividing cancer cells, CTX gets the attention and help of endogenous T cells, and antibiotics reduced that T-cell response, the scientists report.
Their findings in lab animals confirmed the recent work of others that the altered intestinal microbiota impacts CTX’s ability to fight sarcoma, a rare cancer of our connective tissue. Bigger picture, it suggests that some chemotherapy regimens rely on the gut bacteria to stir the immune system to fight cancer, the scientists write.
Human studies are needed to see whether antibiotics affect the outcomes of adoptive T-cell therapy and to give clinicians and their patients better information about how best to maneuver treatment, Zhou notes.