High Fiber Diet May Contribute to Better Immunotherapy Responses in Melanoma

Patients with melanoma who consumed a higher amounts of fiber appeared to have better responses to immune checkpoint inhibitors vs those with a low fiber diet, according to findings from a study published in Science.¹

Results from the study, which assessed patients with melanoma and mouse models, indicated that those who had a high fiber diet and didn’t use over-the-counter probiotic supplements experienced the best responses; probiotic supplement use seemed to lessen the efficacy of immune checkpoint inhibitors somewhat. Moreover, patients who ate at least 20 g of fiber a day had a longer survival without disease progression. Findings from the trial could potentially provide early data on how dietary factors could impact immune responses.

“The data suggest that one can target the composition of the gut microbiota and affect the ability of the patient to respond to immunotherapy,” study co-leader Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology at the National Cancer Institute’s Center for Cancer Research, said in a press release.² “Consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy.”

Although immune checkpoint inhibitors have been efficacious in boosting the immune system’s ability to locate and kill cancer cells, the class of drug can be ineffective at preventing tumors from growing. Previous studies have indicated that bacteria within the gut microbiome may impact immunotherapy responses. In response to this, investigators set out to determine whether altering bacterial composition in the gut microbiome could affect responses to immunotherapy.

Previously, to assess whether PD-1 resistance could be overcome by changing the gut microbiota, investigators used responder-derived fecal microbiota transplants in combination with an anti–PD-1 therapy in patients with PD-1–refractory melanoma.³ The regimen was not only safe in 6 of 15 patients, but was successful in inducing quick and long-lasting microbiota perturbation. Investigators reported an increase in taxa that had previously been associated with response to PD-1 agents, an increase CD8-positive T-cell activation, and a lower occurrence of IL-8–expressing myeloid cells.

Additional findings from the current dietary fiber study, which included a total of 128 patients, indicated that every 5 g increase of daily fiber intake was associated with a 30% decreased risk of disease progression.

Mouse models were used to assess the effect of dietary fiber on PD-1 response. Mice were given either a high fiber or low fiber diet, injected with melanoma, and then treated with a PD-1 therapy. Those that received a high fiber diet experienced a delay in tumor growth vs mice that received a low fiber diet. Mice that had no bacteria in their gut at baseline did not experience a difference in immunotherapy response regardless of dietary fiber.

In the human portion of the study, one-third of patients had reportedly taken probiotics within the last month, although the small sample size and different type of probiotics made it difficult to draw conclusions regarding the association between probiotics and immunotherapy response.

“The impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture. Many factors can affect the ability of a patient with melanoma to respond to immunotherapy. However, from these data, the microbiota seems to be one of the dominant factors. The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics,” Trinchieri concluded.

References

1. Spencer CN, McQuade JL, Gopalakrishnan V, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021;374(6575):1632-1640. doi:10.1126/science.aaz7015
2. A high-fiber diet may improve the response of melanoma patients to immunotherapy. News release. National Cancer Institute. December 23, 2022. Accessed February 9, 2022. https://bit.ly/3oyhmpF
3. Davar D, Dzutsev AK, Mcculloch JA, et al. Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients. Science. 2021;371(6529):595-602. doi:10.1126/science.abf3363