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Fiber helps microbiome boost cancer immunotherapy for melanoma

Checkpoint inhibitors work better with a high-fiber diet, but probiotics don’t help

by Alla Katsnelson, special to C&EN
December 29, 2021


Photo shows an array of high-fiber foods including whole grains, vegetables, and fruits.
Credit: Shutterstock
A high-fiber diet may improve performance of a key type of cancer immunotherapy with the help of the microbiome.

The foods or supplements consumed during cancer therapy can significantly alter its efficacy: A new study in people and mice reports that a high-fiber diet rachets up the tumor fighting power of immunotherapy drugs called checkpoint inhibitors in people undergoing treatment for melanoma, the deadliest form of skin cancer (Science 2021, DOI: 10.1126/science.aaz7015). Common commercially available probiotics do not help, the study found.

“When [cancer] patients ask, “What should I eat, and does it matter?’--well, the answer is probably yes,” says Carrie Daniel-MacDougall, an epidemiologist at MD Anderson Cancer Center who co-led the work. But researchers are just beginning to tease out exactly how–and the new study provides some biological clues.

Checkpoint inhibitors bind to proteins that fine-tune the activity of immune cells called T cells. When the inhibitors bind, they unleash T cells’ ability to kill tumor cells. But these drugs only work in a few types of cancer, including melanoma–and even then, for a minority of patients–though researchers don’t know why.

Recent studies suggest that their efficacy may be linked with the microbiome. A few years ago, Daniel-MacDougall and her colleagues found that people with higher numbers of the Ruminococcaceae family of bacteria in their guts responded better to these drugs when being treated for melanoma (Science 2018 DOI: 10.1126/science.aan4236). So, the researchers set out to track how diet and over-the-counter probiotics, which many people with cancer consume, affect Ruminococcaceae levels and checkpoint inhibitor therapy in people with late-stage melanoma. Of the 128 study participants who provided information about their diets, people who consumed more than 20 grams of fiber per day and who did not take probiotics “had a markedly better response rate than any other patient scenario,” Daniel-MacDougall says. Probiotics didn’t show a clear effect, but the wide range of different probiotics people consumed likely muddied the picture, she says.

Parallel studies in mice showed that mice fed a high-fiber diet fended off melanoma tumors with the help of these drugs significantly better than mice fed a low-fiber diet. The high-fiber diet mice also had higher levels of T cells and higher expression levels of genes related to T cell activity. Dietary fiber normally modulates Ruminococcaceae bacteria, and the results suggest they do so in the context of checkpoint inhibitors, too, Daniel-MacDougall says.

The researchers tested probiotics in mice given checkpoint inhibitors and bolstered by a fecal microbiome transplant from a person who responded strongly to checkpoint inhibitor therapy. In the mice who received probiotics, the drugs didn’t prevent melanoma tumors from growing, but in those who received no probiotics they did. Mice given probiotics also had lower levels of T cells in their tumors.

“We can shift the microbiome with diet, but we need to really understand how predictable and effective that is in the setting of a very strong drug,” Daniel-MacDougall says. The researchers are exploring this relationship more closely in clinical trials in which people undergoing cancer immunotherapy are given a specific diet.

The study shows a clear link between fiber intake and immune response in the tumor, says Jason Locasale, a cancer biologist at Duke University who wasn’t involved in the work. Better understanding of how exactly fiber boosts T cell response–for example, whether features other than the microbiome play a role–may help extend the finding to other types of cancers, he says.


This story was updated on Jan. 4, 2022, to correct the DOI of the 2021 Science paper. It is 10.1126/science.aaz7015, not 10.1126/science.abl6184.


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