Dietary fiber improves outcomes of melanoma patients on immunotherapy

One of the most aggressive cancers, melanoma, is killed by metastasizing, or spreading, to other organs such as the liver, lungs, and brain.

According to a new study, Melanoma patients receiving therapy that makes it easier for their immune system to kill cancer cells respond better to treatment when their diet is rich in fiber.

The study is done by the University of Texas, National Institutes of the Health University of Texas, and National Institutes of Health. Scientists focused on a therapeutic technique called immune checkpoint blockade (ICB). It is a revolutionized treatment of melanoma and cancer in general.

The therapy relies on inhibitor drugs that block proteins called checkpoints produced by specific immune system cells — T cells. These checkpoints prevent immune responses from being too strong, but sometimes that means keeping T cells from killing cancer cells.

Blocked checkpoints lead to better performance of T cells at killing cancer cells.

Morgan said, “ICB has been a game-changer in cancer therapy, and the influence of the gut microbiome on therapeutic response has been demonstrated in numerous studies, in preclinical models, and also in research involving human cohorts. A person’s microbiome is shaped by various environmental factors, including food and medications. At the same time, human genetics accounts for a much smaller proportion of the microbiome variation from person to person.”

“The human gut microbiome is a complicated community of more than 10 trillion microbial cells from about 1,000 different bacterial species. It has remained unclear whether dietary fiber intake and the use of commercially available probiotics affect immunotherapy response in cancer patients.” 

Scientists observed several melanoma patients. They analyzed their gut microbiomes, dietary habits, probiotics, disease features, and treatment outcomes.

Most of the patients were being treated via ICB, typically known as anti-programmed cell death protein therapy, abbreviated to anti-PD-1.

Higher dietary fiber intake is associated with disease non-progression among patients on ICB. The most pronounced benefits were found in patients with dietary solid fiber intake and no probiotic use.

Similar results were demonstrated in the mouse model as well.

Morgan said, “We showed that dietary fiber and probiotic use, both known to impact the gut microbiome, are associated with differing ICB outcomes. From the human cohort results, we can’t assign causality — there may have been other things going on with those patients that we didn’t measure in this study.”

“The results in the mice support the idea that anti-tumor immunity is strongest with a high-fiber diet and no probiotics.”

Scientists invented a computer modeling technique known as transkingdom network analysis for their study. The model integrates multiple types of “omics” data — metagenomic, metabolomic, lipidomic, proteomic, etc., to determine how interactions among specific types of gut microbes help or hinder biological functions in the host. In this case, the microbial interactions involved how well the host responds to immune checkpoint blockade.

Morgan said, “It’s important to note that transkingdom network analysis in mice showed a family of bacteria, Ruminococcaceae, among the organisms increased by the high-fiber diet; the same bacteria were found in the current study involving humans and in previous, related research with people.”

“Double-blind, randomized dietary intervention studies will be critical for establishing whether a targeted, achievable diet change at the start of ICB therapy can improve patient outcomes.”

“And though the findings suggest that some commercially available probiotics may be harmful to patients on ICB, more research is needed to determine which probiotics could be beneficial.”

Journal Reference:

1. Christine N. Spencer, Jennifer L. McQuade et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science, 2021; 374 (6575): 1632 DOI: 10.1126/science.aaz7015