Supplement, keto diet may boost immunotherapy

Immunotherapy is a treatment that uses the body’s immune system to fight cancer.

There are currently two types of immunotherapy available for prostate cancer — cancer vaccines and immune checkpoint inhibitors.

“Immunotherapy, through inhibiting T-cell immune checkpoint pathways — PD1 or CTLA4 — has revolutionized many [therapies for] other cancer types [too],” Xin Lu, PhD, the John M. and Mary Jo Boler collegiate associate professor in the Department of Biological Sciences at the University of Notre Dame, IN, and corresponding author of this study explained to Medical News Today.

“However, advanced prostate cancer remains resistant to it,” he added.

“This is likely due to an increase of pro-tumor immune cells coupled with insufficient tumor-specific antigens that the immune system can recognize to kill the cancer cells,” Lu explained. “Therefore, we need to find new ways to sensitize prostate cancer to immunotherapy.”

For this study, researchers examined what would happen if they added a pre-ketone supplement to immunotherapy for prostate cancer.

According to Sean Murphy, PhD candidate in the Lu Lab in the Department of Biological Sciences at the University of Notre Dame and first author of this study, the idea to use a pre-ketone supplement came from an observation that an epigenetic drug — so-called HDAC inhibitor — was able to sensitize prostate cancer models to immunotherapy.

There were also previous reports that ketogenic diets can produce ketone body beta-hydroxybutyrate (BHB), which has HDAC inhibitor-like properties.

“We tried both [a] ketogenic diet and pre-ketone BHB-generated supplement, with the latter being potentially more practical for a patient to use in a clinic,” Murphy told us. “Another reason to use [a] pre-ketone supplement is to determine if the presence of BHB was sufficient to enhance immunotherapy in the mouse models.”

“With pre-ketone supplement showing an even better response in our study, we conclude that the presence of BHB, rather than extremely low carbohydrate, was the key factor to drive better response to immunotherapy,” he added.

Lu, Murphy, and their colleagues explored their hypothesis via a mouse model of prostate cancer. They divided the mice into six groups.

Three of the groups received only immunotherapy, only a keto diet, or only a pre-ketone supplement. Two more groups were given a combination of the keto diet and immunotherapy or the pre-ketone supplement plus immunotherapy. The sixth group was the control group.

At the study’s conclusion, the researchers found there was no change in tumors in the immunotherapy-only group.

Both the pre-ketone-supplement-only approach, and the combination of keto diet and immunotherapy reduced cancer tumors and extended the lives of the mice.

Overall, the scientists found that the group with the combination of pre-ketone supplement and immunotherapy had the best outcomes, with 23% of the mice becoming tumor-free.

“The pre-ketone supplement does two things to enhance immunotherapy,” Lu explained.

“First, it makes cancer cells more detectable to the immune system by increasing the presentation of molecular features on the surface of cancer cells. Second, ketone body from the supplement, together with the immunotherapy, elicit special metabolic and molecular effects on immune cells so the cells are doubly stimulated to attack the cancer, potentially clearing it.”

– Xin Lu, PhD

“The 23% cure rate certainly brought a lot of hope at this preclinical stage, because patients with castration-resistant prostate cancer have no curative treatment in the clinic,” Murphy said.

“Of course, we also understand 23% is not a high number. There is still room to increase this number by optimizing the combination and possibly adding another therapy,” he admitted.

MNT also spoke with Wael Harb, MD, a board-certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain Valley, CA, about this study.

Harb, who was not involved in this research, said he found the idea of combining a ketogenic diet or ketone supplement and immunotherapy to potentially enhance the efficacy of checkpoint blockade therapy in prostate cancer intriguing.

“As we all know, prostate cancer has been notoriously resistant to therapies, but the use of immunotherapy has shown us more success in other types of cancerl, such as melanoma and lung cancer,” he noted.

However, to anyone thinking that following the keto diet or adding a pre-ketone supplement to their diet might help decrease their prostate cancer risk, Harb said to remember the human body is complex and when you do a study like this, it does not necessarily translate to the keto diet being able to treat cancer.

“The study, I would say, at best at this point [in] time raises the interest in exploring that [possibility] clinically, but it’s not anywhere close to making a recommendation for patients as far as to fight cancer or prevent cancer,” Harb cautioned.

“I would like to see a clinical trial — moving from animal models to human clinical trials is essential in developing efficacy and safety and that’s something really needed. [And] if this is true for prostate cancer, it might be true for other cancers — we need to look into other tumor types,” he added.

“And I think we need to look into the diet even more carefully — how much ketosis would we need to induce?” Harb wondered.

He also emphasized that:

“We have to be careful for patients with cancer — we don’t want them to lose weight. The ketogenic diet can lead to weight loss, and weight loss can be detrimental for somebody who has cancer. […] So can we induce [a] ketogenic rate without making them lose weight? There needs to be some middle ground where we’re able to maintain weight and muscle mass while we are helping overcome the resistance to immunotherapy.”