Could antibiotics help boost resistance to pancreatic cancer?

By David Douglas

NEW YORK (Reuters Health) - Eliminating certain bacteria in mice with pancreatic cancer slowed tumor growth and helped restore the ability of the immune system to fight the disease in a new study.

"The clinical implications are that one must account for the microbiome when administering immunotherapy as manipulating the microbiome can alter the response to treatment," Dr. Mautin Hundeyin of New York University School of Medicine told Reuters Health by email. "Ablating the bacteria in patients can make immunotherapies effective against pancreatic cancer."

Dr. Hundeyin and colleagues studied both mice and patients with pancreatic ductal adenocarcinoma (PDA). As they report in Cancer Discovery, online March 22, they found that "the cancerous pancreas harbors a markedly more abundant microbiome compared to normal pancreas in both mice and humans, while select bacteria are differentially increased in the tumorous pancreas compared to gut."

The researchers established that an ablative oral antibiotic regimen in mice led to a reduction of tumor burden of about 50%. "Ablation of the microbiome," they point out "protects against pre-invasive and invasive PDA, whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor-protection."

The researchers also determined that Proteobacteria, Actinobacteria, Fusobacteria and Verrucomicrobia were each higher in the gut of PDA patients than in healthy controls. Moreover, they observe, "Proteobacteria was also enriched in the intra-pancreatic microbiome in PDA bearing patients and was associated with advanced disease."

They further determined that the "distinct and abundant microbiome drives suppressive monocytic cellular differentiation in pancreatic cancer via selective toll-like receptor ligation leading to T cell anergy."

Targeting this microbiome, they add, "protects against oncogenesis, reverses intra-tumoral immune-tolerance, and enables efficacy for check-point based immunotherapy"

In a statement, co-author Dr. Deepak Saxen of the NYU College of Dentistry concluded, "Studies already underway in our labs seek to confirm the bacterial species most able to shut down the immune reaction to cancer cells, setting the stage for new bacteria-based diagnostic tests, combinations of antibiotics and immunotherapies, and perhaps for probiotics that prevent cancer in high-risk patients."

SOURCE: https://bit.ly/2q5D1H3

Cancer Discovery 2018.

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