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Restricted Protein Diet Improves Immunotherapy Response in Mice

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Roberto Pili, M.D., the Robert Wallace Miller Professor of Oncology at Indiana University School of Medicine and a researcher at the Indiana University Melvin and Bren Simon Cancer Center, and colleagues have previously found that cutting protein from the diets of mice models with prostate cancer and breast cancer slowed the growth of their tumors.

In the most recent study, the research group reported that by cutting protein intake from 20 percent to 10 percent the mice models responded better to immunotherapy. Immunotherapy is a treatment that uses the immune system to fight diseases such as cancer.

“This is important because today’s immunotherapy, like immune checkpoint inhibitors, are really becoming the standard of care for many solid tumors. We believe this is applicable to a broad spectrum of patients with different types of cancer,” said Pili, a nationally recognized expert in prostate, renal and bladder cancers.

The research was published online Sept. 6 in the journal Clinical Cancer Research.

Typically a person undergoing cancer treatment would be advised to eat a high-protein diet because of weight loss that usually happens while in treatment.

However, Pili’s initial research supports the hypothesis that by incorporating a modification to a patient’s diet, such as restricting the amount of proteins in their diets even for a limited period, a patient may still benefit from immunotherapy.

“Our goal is to look at how we can modify a person’s diet who already has cancer and make this diet modification benefit them,” Pili said.

Why the protein restriction? Pili pointed to evidence that people whose diets are high in protein--animal fat, dairy products and red meats--have a higher incidence of cancer. Meanwhile, diets that are plentiful with vegetables, legumes and fish are associated with lower incidence of cancer.

Dr. Pili likened the restricted protein diet to releasing a brake as it may help to decrease the immunosuppression that some cancer patients have.

“The immunosuppression might be why some patients don’t respond to immunotherapy because the current drugs, such as immune checkpoint inhibitors, release the brake on the immune system. If the brake is not released completely, the drugs don’t work. If we help to reduce the effect of the brake with diet, we might actually subdue the immunosuppression mechanisms and better unleash the immune response,” he said.

Pili added: “This study demonstrates that additional research is needed so we can continue to learn more about the role of diet modifications, particularly protein restriction, and immunotherapy in cancer patients. Our initial results suggest that dietary modifications may lead to better responses to immunotherapies, which may lead to less invasive treatments down the road.”

Pili is the principal investigator of a clinical trial that is open at the IU Simon Cancer Center for prostate cancer patients who are receiving immunotherapy. In the trial, patients will randomly be selected for a normal protein diet or a reduced protein diet.   

Pili is also professor of medicine and of urology at IU School of Medicine and a co-leader of the Experimental and Developmental Therapeutics (EDT) research program at the IU Simon Cancer Center. Researchers in that program work to move cancer therapies from the laboratory bench to the bedsides of patients.

This article has been republished from materials provided by Indiana University. Note: material may have been edited for length and content. For further information, please contact the cited source.


Orillion, A. R., Damayanti, N. P., Shen, L., Adelaiye-Ogala, R., Affronti, H. C., Elbanna, M., . . . Pili, R. (2018). Dietary protein restriction reprograms tumor associated macrophages and enhances immunotherapy. Clinical Cancer Research. doi:10.1158/1078-0432.ccr-18-0980