A growing body of evidence links the microbiome, which can be altered by diet, with response to cancer immunotherapy. A more difficult task is teasing out the mechanism by which diet might be used to improve immunotherapy outcomes.

“When we think of tumor response to immunotherapy, we traditionally think about the tumor and the tumor microenvironment,” said Jennifer McQuade, MD, University of Texas MD Anderson Cancer Center. “The role of the host has not been studied until quite recently. We can’t change host factors such as age and sex, but we can change diet. The microbiome has become a therapeutic target.”

McQuade spoke Friday, April 8, during the Educational Session Diet, Microbiota, and Cancer Immunotherapies, which explored the links between dietary modification of the microbiome and response to immunotherapy. The session can be viewed on the virtual platform by registered meeting participants through July 13, 2022.

In mice, fecal microbiota transplantation (FMT) can promote immunotherapy resistance to immunotherapy response. Observational studies in humans show strong associations between gut microbiome composition and immunotherapy response.

FMT can double response rates in anti-PD1-refractory melanoma in humans from 10-15 percent to about 30 percent, McQuade said. However, FMT also raises multiple questions about donor selection, scalability, procedural risks, and potential transfer of other diseases, she added.

Probiotics, or bacterial supplementation, can alter the microbiome, but may or may not have a significant impact on treatment response.

Early work in modifying diet to alter the microbiome is promising, McQuade noted. Observational studies showing an association between longer progression-free survival following anti-PD-1 therapy for melanoma and greater diversity in gut microbiota have led to controlled feeding studies testing diet as a drug.

A phase I trial in melanoma survivors found that a diet providing at least 50 grams of fiber daily is tolerable with excellent compliance. Microbiota abundance and diversity improved, McQuade reported, but changes were heterogeneous across the patient population.

Altering the diet brought notable changes to the circulating metabolome, with elevated levels of positive lipids and tryptophan/indoles, and reduced levels of bile acids and inflammatory metabolites. A phase II study of diet and immune effects is currently enrolling melanoma patients.

“Diet change is hard,” McQuade said. “You need long-term change in diet to make sustained changes in the microbiome. A reductionist approach—better understanding the interactions between diet, microbiome, and immune response to rationally design prebiotics—has a lot of appeal. It is easier to take a pill than to change your diet.”

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