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Giving common antibiotic before radiation may help body fight cancer

Penn study finds vancomycin's effect on gut microbiome in mice can boost immune response

University of Pennsylvania School of Medicine

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IMAGE: The antibiotic vancomycin alters the gut microbiome in a way that can help prime the immune system to more effectively attack tumor cells after radiation therapy. view more 

Credit: Penn Medicine

PHILADELPHIA - The antibiotic vancomycin alters the gut microbiome in a way that can help prime the immune system to more effectively attack tumor cells after radiation therapy. A new study in mice from researchers at the Abramson Cancer Center of the University of Pennsylvania found giving a dose of the common antibiotic not only helped immune cells kill tumors that were directly treated with radiation, but also kill cancer cells that were further away in the body, paving the way for researchers to test the approach in a human clinical trial. The Journal of Clinical Investigation published the findings today.

More than half of all patients with solid tumors undergo radiation therapy at some point during their treatment. In recent years, multiple studies have shown that giving patients higher doses of radiation over the course of fewer treatments - called hypo-fractionated radiotherapy - can induce a stronger immune response in patients. In addition, hypo-fractionated doses have the ability to impact other tumors cells in the body that weren't directly treated with radiation. This is known as the abscopal effect.

"Our study shows that vancomycin seems to boost the effect of the hypo-fractionated radiation itself on the targeted tumor site while also aiding the abscopal effect, helping the immune system fight tumors away from the treatment site," said the study's senior author Andrea Facciabene, PhD, an associate professor of Radiation Oncology in Penn's Perelman School of Medicine.

Facciabene and his team chose vancomycin for a few specific reasons. First, it mostly targets gram-positive bacteria, making it disruptive to the gut microbiome. Second, it's a large molecule, which means it stays in the gut and does not circulate to the rest of the body the way other antibiotics do. The fact that it is not systemic limits the impact it has on the rest of the body's microbiome.

In this study, researchers found vancomycin specifically improved the function of dendritic cells, which are the messenger cells that T cells rely on to know what to attack. While researchers used melanoma, lung, and cervical cancer models for this work, they note the approach could have implications for a wide variety of cancer types. This study also builds off the team's previous research, which showed a similar effect in T cell therapies, meaning it adds to a growing body of evidence.

Still, the researchers note this study only scratches the surface when it comes to understanding the connection between the makeup of the gut microbiome and its impact on radiotherapy-induced immune responses to cancer. They say further research is needed to understand the implications of specific strains or clusters of bacteria.

"However, what's clear is that antibiotics play a role and can potentially impact treatments and outcomes for cancer patients," Facciabene said. The researchers are planning a phase 1 study to translate this approach into the clinic.

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Other Penn authors on the study include co-lead authors Mireia Uribe-Herranz, Stavros Rafail, Silvia Beghi, and Luis Gil-de-Gómez, as well as co-authors Ioannis Verginadis, Sergey Pustylnikov, Stefano Pierini, Renzo Perales-Linares, Ian A. Blair, Clementina A. Mesaros, Frederic Bushman, and Constantinos Koumenis.

The study was supported by the National Institutes of Health (R01CA219871-01A1)

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $425 million awarded in the 2018 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center--which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report--Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation's first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Home Care and Hospice Services, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 40,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2018, Penn Medicine provided more than $525 million to benefit our community.

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