Potential of manipulating gut microbiome to boost efficacy of cancer immunotherapies

April 02, 2018

PHILADELPHIA -The composition of bacteria in the gastrointestinal tract may hold clues to help predict which cancer patients are most apt to benefit from the personalized cellular therapies that have shown unprecedented promise in the fight against hard-to-treat cancers, according to new research from the Perelman School of Medicine at the University of Pennsylvania.

Reporting in the Journal of Clinical Investigation Insights, a team led by senior author Andrea Facciabene, PhD, a research assistant professor of Radiation Oncology and Obstetrics/Gynecology, found that the effectiveness of adoptive T cell therapy (ACT) in mice with cancer is significantly affected by differences in the natural makeup of gut bacteria and treatment with antibiotics. The team also found that the use of fecal transplants - which are increasingly used for treating recurrent C. difficile colitis - affected the efficacy of ACT between different strains of lab rodents. ACT enlists a patient's own immune system to fight diseases, such as cancer and certain infections. T cells are collected from a patient and grown in the lab to increase the number of tumor-killing T cells. . The pumped-up cells are then given back to the patient as reinforcements to the body's natural anti-tumor immune response.

Experiments performed by coauthor Mireia Uribe-Herranz, PhD, a research associate in Facciabene's lab, demonstrate that when ACT was performed on genetically identical animals obtained from different vendors (Jackson Laboratory or Harlan Laboratories), which carry different microbiota, impact of the therapy was not identical. Animals obtained from Harlan showed a much stronger anti-tumor effect compared to animals from Jackson.

Depletion of gram-positive bacteria within the gut, using an antibiotic called vancomycin, also increased the efficacy of the therapy, improving the anti-tumor response and overall remission rate in less-responsive mice. The beneficial responses were associated with an increase in systemic dendritic cells, which in turn increased the expression of interleukin 12 (IL-12), which sustained expansion and anti-tumor effects of transferred T cells.

To define a relationship between gut bacteria and the efficacy of ACT, the researchers transplanted fecal microbiota from Jackson mice to Harlan mice. They found that Harlan mice transplanted with Jackson microbiota copied the anti-tumor response and tumor growth of Jackson mice.

"This means that the microbiota-dependent response to ACT was successfully transferred between mice, and that modulation with specific antibiotics can be used to increase ACT efficacy," Facciabene said, confirming that this technique could be applied to control gut microbiome populations and improve ACT. Collectively, the findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT.
-end-
This research was supported by Be the Difference Foundation, Teal Tea Foundation, and the Pennsylvania Department of Health.

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 the past 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 $405 million awarded in the 2017 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; Penn Wissahickon Hospice; and Pennsylvania Hospital - the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine, and Princeton House Behavioral Health, a leading provider of highly skilled and compassionate behavioral healthcare.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2017, Penn Medicine provided $500 million to benefit our community.

University of Pennsylvania School of Medicine

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.