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Diet, supplements may affect immunotherapy response among patients with melanoma
Patients with melanoma who consumed high-fiber diets appeared to have better responses to anti-PD-1 immunotherapy than those who ate less fiber, according to study results scheduled for presentation at American Association of Cancer Research Annual Meeting.
The high-fiber diet appeared associated with higher gut microbiome diversity, which may facilitate responses to checkpoint inhibitors.
“What we found in profiling patients prior to therapy is that certain features of the gut microbiome were associated with response,” Christine Spencer, PhD, research scientist at Parker Institute for Cancer Immunotherapy, said during a press cast. “While the data is still early, we found that patients eating high-fiber diets were about five times as likely to respond to anti-PD1 checkpoint blockade immunotherapy.”
Previous studies have concluded that patients with melanoma and a diverse gut microbiome — specifically with enriched “pro-response” bacteria from the Ruminococcaceae family — are more likely to respond to anti-PD-1 treatment.
Spencer and colleagues sought to analyze how diet and supplements affected the gut microbiome and responses to checkpoint immunotherapy.
Researchers analyzed fecal samples from 113 patients with melanoma and collected diet information via a questionnaire. Researchers also asked patients about probiotic and antibiotic use.
Overall, baseline alpha diversity appeared highest among patients who achieved partial or complete response (mean, 355), followed by those with stable disease (mean, 330) and progressive disease (mean, 318).
Researchers observed associations between higher microbiome diversity and therapy responses regardless of treatment, with no significant differences in gut microbiome by age, sex or BMI.
More than 40% of the patients reported use of probiotic supplements and 29% reported antibiotic use, both of which appeared associated with lower alpha diversity of the gut microbiome (P = .02).
“Patients should have conversations with their doctors before taking over-the-counter probiotic supplements,” Spencer said. “A lot of people have the perception that probiotics will provide health benefits, but that might not be the case in patients [with cancer]. We’re not saying all of them are bad, but the message is that these factors have never been studied in patients on immunotherapy, and our data suggests for the first time that they could matter.”
Results from a subset of patients (n = 46) using anti-PD1 therapy showed that patients with high-fiber diets had a higher chance of responding to immunotherapy than patients with low-fiber diets (OR = 5.3; 95% CI, 1.02-26.3). Specifically, whole grains and overall diet quality correlated positively with pro-response bacteria.
Patients who reported high consumption of processed meat and added sugar had fewer of the pro-response bacteria in their gut microbiomes.
A joint effects analysis indicated patients with a favorable (T1) gut microbiome signature and a high-fiber diet had the greatest odds of responding to treatment (OR = 3.6; 95% CI, 0.7-17.8) compared with patients with a low-fiber diet and without a T1 signature (OR = 1.9; 95% CI, 0.6-6.4).
“We know from prior research that eating a high-fiber diet has a lot of health benefits,” Spencer said. “But with this preliminary research on patients [with cancer] and the microbiome, it appears that fiber is also linked to a better response to immunotherapy.” – by John DeRosier
Reference:
Spencer C, et al. Abstract 2838/24. Scheduled for presentation at: AACR Annual Meeting; March 29-April 3, 2019; Atlanta.
Disclosures: Spencer reports consultant/advisory roles with The University of Texas MD Anderson Cancer Center and contributing to a U.S. patent application submitted by MD Anderson Cancer Center that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Please see the abstract for all authors’ relevant financial disclosures.
Perspective
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Understanding how gut bacteria influences cancer development and response to therapy is an exciting area that’s emerging in cancer research. It’s exciting from my point of view to learn that patients and healthy individuals can also be empowered through their diet to control cancer development and influence their response to therapies.
I caution that this is still early — we need to better understand which bacteria are good and which are bad — and we don’t really have the best handle on the mechanisms yet. But this research suggests that a high-fiber diet is associated with a response to therapy. As we already know, high-fiber diets are associated with reduced incidences of some cancers.
Diet is important in preventing diabetes and obesity, which are both risk factors for cancer. These new data provides some possible mechanisms to explain why high-fiber diets can be beneficial to patients with cancer.
This study also underscores the importance of more research in this area. Patients need to understand that we don’t know a lot about the bacteria in the GI tract and that it can be detrimental when we take over-the-counter supplements, such as probiotics.
What’s also interesting is that the gut bacteria is affecting cancers that are not necessarily derived from the gut, so the microbiome has importance in probably many different cancers and their therapies.