Could probiotics reduce immunotherapy’s chances of working in cancer patients?

Study suggests yes, also links high fiber diet to better response to checkpoint inhibitor treatment

Parker Institute for Cancer Immunotherapy findings on microbiome, diet and checkpoint inhibitors to be presented at SITC 2018, Nov. 9-11, 2018

Research by Parker Institute for Cancer Immunotherapy scientists suggests that probiotics may negatively impact the gut microbiome’s makeup and diversity, potentially reducing a cancer patient’s ability to respond to checkpoint inhibitor treatment.

While checkpoint inhibitors are considered a breakthrough for cancer – and most recently became the subject of the Nobel Prize for medicine – this type of immunotherapy treatment only works for 20 to 30 percent of cancer patients.

Researchers remain on the hunt for answers as to why, and recently found that a person’s gut microbiome may play a role. These new findings on diet, probiotics and antibiotics add another layer of complexity to the discussion.

“While preliminary, these results point to the idea that taking probiotics could make checkpoint inhibitors less effective for treating cancer due to changes in the gut microbiome,” said Christine Spencer, Ph.D., a research scientist at the Parker Institute and co-first author on the research. “This was a surprise to us because probiotics are commonly viewed as promoting gut and overall health. However, in this instance the data suggest that’s not necessarily the case.”

This is the first study to explicitly look at the connections between the microbiome, dietary factors and cancer immunotherapy efficacy in patients. The results are being presented as a poster at the Society for Immunotherapy of Cancer (SITC) annual meeting, being held at the Walter E. Washington Convention Center in Washington, D.C., from November 9 through November 11.

The microbiome and cancer immunotherapy connection

Cancer immunotherapy drugs such as checkpoint inhibitors work by engaging the immune system to fight off cancer. The immune system is heavily moderated by trillions of microbes in the gut that make up the microbiome.

One hypothesis is that changes to the microbiome could affect the immune system, and in turn, the ability for immunotherapy to work against cancer.

That is what Parker Institute investigator Jennifer Wargo, M.D., of The University of Texas MD Anderson Cancer Center demonstrated in a 2017 paper in Science. Her team showed 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, such as Faecalibacterium, were linked to better outcomes.

They also found that changing a mouse’s microbiome to a “good” microbiome with a fecal transplant was associated with a better response to checkpoint inhibitors.

The study prompted the question of whether changing the human microbiome through diet or medication use could also influence a cancer patient’s response to checkpoint inhibitor drugs.

As a follow-up, Spencer, Dr. Wargo and their colleagues began to examine the role of diet and the microbiome in cancer immunotherapy.

Diet, the microbiome and checkpoint inhibition

The study involved 312 melanoma patients who were starting checkpoint inhibitor therapy. A subset self-reported on their dietary habits, including consumption of red meat, sugary beverages, fiber, and the use of probiotics and antibiotics.

More than 40 percent who took the survey reported taking probiotics. The use of probiotics prior to starting therapy was linked to a less diverse microbiome.

Taking probiotics was also associated with lower odds for responding to checkpoint inhibitor treatment compared to those not taking biotics at all.

Spencer stressed that these initial findings need to be researched further before recommendations to patients can be made.

“While this data provides some insights, we need to do additional studies before anyone can make definitive guidelines for patients on what dietary supplements are or aren’t beneficial when undergoing checkpoint therapy,” Spencer said.

High fiber good for gut

One dietary factor that appeared to boost the chances that immunotherapy may work is fiber intake.

Patients who reported eating a high fiber diet had more types of microbes and were more than five times as likely to respond to checkpoint inhibitor drugs targeting PD-1, a protein on the surface of tumor cells.

“In our study a high fiber diet was linked to a healthier gut microbiome, and also better patient response to anti-PD-1 checkpoint inhibitors,” Spencer said.

“We have a lot more to learn, but the bottom line is that what you eat and drink could impact your ability to respond to immunotherapy treatments if you have cancer,” said Theresa LaVallee, Ph.D., Parker Institute vice president of translational medicine and regulatory affairs. “This is a new and important area of study, and findings like these will help inform our upcoming clinical trial that will evaluate if we can translate Dr. Wargo’s prior findings to cancer patients.”

Vancheswaran Gopalakrishnan, MPH, Ph.D., and Jennifer McQuade, M.D., of MD Anderson contributed equally as first authors of the poster. Dr. Wargo is senior author.

The Parker Institute is working on a clinical research project with Dr. Wargo and Seres Therapeutics to further evaluate whether changing the microbiome using fecal transplant or other means could alter patient response to checkpoint inhibitors. Read more about the Parker Institute’s work on cancer immunotherapy and the microbiome.