Probiotics Linked to Poorer Response to Cancer Immunotherapy in Skin Cancer Patients

Study to be presented by Parker Institute researchers at AACR 2019 also finds eating fiber tied to better outcomes

In melanoma patients, taking over-the-counter probiotic supplements was associated with a 70 percent lower chance of response to cancer immunotherapy treatment with anti-PD-1 checkpoint inhibitors, according to a preliminary study from the Parker Institute for Cancer Immunotherapy (PICI) and The University of Texas MD Anderson Cancer Center. The results are being presented today at the American Association for Cancer Research (AACR) 2019 Annual Meeting in Atlanta.

Researchers also found that probiotics were linked to lower diversity in the gut microbiome, previously found to be associated with poorer immunotherapy response.

“These findings about probiotics were a bit surprising to us because the general perception is they make your gut microbiome healthier,” said first author Christine Spencer, Ph.D., a research scientist at the Parker Institute, based in San Francisco. “While more research is needed, our data suggests that may not be the case for cancer patients.”

Probiotics are not regulated by the U.S. Food and Drug Administration.

“Based on our early results, cancer patients and doctors should carefully consider the use of over-the-counter probiotic supplements, especially before beginning immunotherapy treatment,” said senior author Jennifer Wargo, M.D., MMsc, a PICI investigator at MD Anderson.

This is the first clinical study designed to examine the relationships between diet, the gut microbiome and immunotherapy response in cancer patients. In addition to the probiotics findings, the data also show patients who reported eating a high-fiber diet were five times as likely to respond to cancer immunotherapy.

POTENTIAL IMPACT OF THE RESEARCH

The implications of the research are significant because checkpoint inhibitors –  a Nobel Prize-winning type of cancer immunotherapy treatment – only work for 20 to 30 percent of cancer patients. The research bolsters the idea that cancer patients might be able to improve how well immunotherapy treatment works by eating, drinking – or avoiding – certain foods, beverages and supplements.

“Imagine if you could increase the number of patients who benefit from immunotherapy through something as simple as dietary changes. That would be remarkable,” Spencer said. “It’s probably not going to be that simple, as there are many factors at work. But this study does point to diet playing a role in immunotherapy response via the gut microbiome and we hope these findings will spur more studies on this topic in the cancer research community.”

THE MICROBIOME-CANCER IMMUNOTHERAPY CONNECTION

In recent years, scientists have discovered that the trillions of intestinal microbes that make up the gut microbiome exert significant control over the immune system. Cancer immunotherapy drugs such as checkpoint inhibitors work by engaging the immune system to fight off cancer.

In theory then, the makeup of the microbiome could affect the immune system, and in turn, the ability for immunotherapy to work against cancer.

A prior study by Dr. Wargo and Spencer was one of the first to explore that idea. In their 2018 Science paper, they and colleagues at MD Anderson found that a more diverse array of microbes in the gut was associated with better response to checkpoint inhibitors for cancer, and that certain types of bacteria in the Ruminococcaceae family were associated with a better response to anti-PD-1 checkpoint inhibition. Other types of bacteria, such as those in the order Bacteroidales, were linked to a poorer outcome.

“There were different types of microbiome profiles, if you will, that were linked to better or poorer response to checkpoint inhibition,” said Dr. Wargo. “For this new study on the diet, microbiome and immunotherapy, we used profiles of responders as the mark of a “good” microbiome when it comes to immunotherapy response.”

ABOUT THE STUDY

The prospective study involved 113 metastatic melanoma patients who were starting treatment at MD Anderson in Houston. The researchers prospectively evaluated their microbiomes by sequencing their fecal samples to determine the presence and abundance of various bacteria in the gut. Patients were also asked to take a lifestyle survey to report on their diet and use of supplements and medication.

After following patients through treatment, the researchers found several correlations between dietary factors and the gut microbiome. They also evaluated those factors in relation to immunotherapy response in a subset that went on anti-PD-1 checkpoint inhibitors.

KEY FINDINGS

Overall, Parker Institute and MD Anderson researchers found that diet and supplements appear to have an effect on a patient’s ability to respond to cancer immunotherapy, most likely due to changes in the patient’s gut microbiome.

Among the findings:

• Over-the-counter probiotic supplement use was linked to a 70% lower chance of response to immunotherapy with anti-PD-1 checkpoint inhibitors in a subset of 46 melanoma patients
• 42% of all patients reported taking over-the-counter probiotics among those who took the lifestyle survey
• Probiotics were linked to lower gut microbiome diversity, previously shown to be associated with poorer response to anti-PD-1 checkpoint inhibitors
• Patients eating high-fiber diets were about 5 times as likely to respond to immunotherapy treatment with anti-PD-1 checkpoint inhibitors
• Patients eating diets rich in whole grains had more bacteria associated with positive response to checkpoint immunotherapy
• Diets high in processed meat and added sugar had fewer bacteria associated with a positive response to checkpoint immunotherapy

“Eating a high-fiber diet has long been shown to have health benefits. In this case, we see signs that it is also linked to a better response to cancer immunotherapy,” Spencer said. “Definitely another good reason to load up on whole grains, vegetables and fruits.”

ADDITIONAL MICROBIOME-CANCER IMMUNOTHERAPY TRIALS UNDERWAY

While this study focused on correlations rather than root cause, other randomized, controlled clinical trials are underway that are designed to directly answer the question of whether one can manipulate the microbiome – through food, fecal transplant or other means – to improve cancer immunotherapy response.

The Parker Institute is now conducting such a trial in collaboration with MD Anderson and Seres Therapeutics. This randomized, placebo-controlled clinical study is evaluating whether a specially designed oral microbiome pill with specific types of bacteria could positively impact a patient’s response to checkpoint inhibitors.

The study is open at MD Anderson and the Angeles clinic. For additional information on this trial (NCT03817125) please visit www.clinicaltrials.gov.

In addition, a team of MD Anderson researchers is planning a prospective randomized study in which cancer patients will be provided with different types of diets. Their gut microbiomes will be sequenced to see if and how they change. The study will also evaluate treatment response to immunotherapy.

Abstract 2838: “The gut microbiome (GM) and immunotherapy response are influenced by host lifestyle factors”

Spencer is presenting the most up-to-date information during the Inflammation and Microbiome poster session that runs from 8 a.m.-12 p.m. EDT, April 2, 2019 at the AACR 2019 Annual Meeting.  

Contact Information

For more information or a copy of the poster, please contact Science Communications Manager Shirley Dang, sdang@parkerici.org, 415-930-4385.