Antibiotics influence cancer treatment efficacy

Washington D.C.: Turns out, antibiotics may impact cancer treatment efficacy.

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, said Dr Gang Zhou, in a study conducted at Medical College of Georgia at Augusta University.

Antibiotic use is known to have a near-immediate impact on our gut microbiota and long-term use may leave us drug-resistant and vulnerable to infection.

"It likely depends on what types of therapy physicians are giving to patients and how often they also are giving them antibiotics," said Zhou, corresponding author of the study.

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.

"We give a lot of medications to prevent infections," said Dr Locke Bryan, a study co-author.

"White blood cell counts can go so low that you have no defence against bacteria, and that overwhelming infection can be lethal," said Bryan.

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 consequently, some therapies might be too.

They reported 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.

"These infused T cells can pretty much act on their own to kill cancer cells", Zhou said.

With this approach, physicians retrieve T cells from a patient's blood, engineer them to express a tumour-finding receptor - called chimeric antigen receptor, or CAR - and give them back to the patient.

These patients typically will receive a conditioning chemotherapy regimen, which often includes the common agent cyclophosphamide, or CTX, to intentionally wipe out some of their normal T cells and make room for the engineered super-fighters.

This emerging treatment is often used in patients, who have failed multiple other treatments, including chemotherapy.

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 mimicked therapy in which receptors that target the patient's tumour are put into their T cells.

In this case, the researchers transferred tumour-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 a tumour, now that they can better target it", Zhou said.

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 reported.

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 suggested that some chemotherapy regimens rely on the gut bacteria to stir the immune system to fight cancer, the scientists wrote.

"It is clear in animal models that if you wipe out the intestinal microbiota like you do with antibiotics, it will attenuate the chemotherapy efficacy," said Zhou. "There is also emerging clinical evidence showing that for CTX-based chemotherapy, some patients who also get antibiotics for a longer period of time seem to have less optimal outcomes."

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 manoeuvre treatment, Zhou noted.

The study is published in the journal Oncotarget.