Study Shows Potential of Ketogenic Diet Component Combined with Immunotherapy in Prostate Cancer Treatment

by Ella

Researchers at the University of Notre Dame have made a significant breakthrough in prostate cancer treatment by combining a pre-ketone supplement with immunotherapy, according to a recent study published in Cancer Research.

Prostate cancer has historically shown resistance to immune checkpoint blockade (ICB) therapy, a form of immunotherapy that targets specific proteins to activate the body’s immune response against cancer cells. Lead researcher Xin Lu, along with collaborators, sought to address this challenge by exploring the potential synergy between a pre-ketone supplement and ICB therapy.


Lu, the John M. and Mary Jo Boler Collegiate Associate Professor in the Department of Biological Sciences, explained, “Prostate cancer is the most common cancer among American men, but traditional immunotherapy has shown limited effectiveness in treating it. We aimed to investigate whether combining a dietary supplement with immunotherapy could enhance treatment outcomes.”


The study, led by ’24 alumnus Sean Murphy, who was a doctoral student in Lu’s lab, focused on depriving mouse models of carbohydrates—a fundamental aspect of the ketogenic diet. The models were divided into different groups, including those receiving immunotherapy alone, a ketogenic diet alone, a pre-ketone supplement alone, and various combinations of these interventions alongside immunotherapy.


Results showed that while immunotherapy alone had minimal impact on tumor growth, the combination of the ketogenic diet or pre-ketone supplement with immunotherapy significantly reduced cancer progression and extended the lifespan of the mouse models. Notably, the supplement combined with immunotherapy demonstrated the most promising results, with 23% of mice achieving complete tumor regression.


According to Lu, the key mechanism behind this success lies in the presence of ketone bodies, which are produced in the body during ketosis—a state induced by the ketogenic diet or pre-ketone supplements. Ketones disrupt the metabolic cycle of cancer cells, rendering them more susceptible to immune attack by T cells.

“This study underscores the potential of ketone supplementation to sensitize prostate cancer cells to immunotherapy,” Lu emphasized. “By altering the tumor microenvironment, ketones facilitate T cell infiltration and enhance their anti-cancer activity.”

The researchers further validated their findings through single-cell RNA sequencing, which revealed significant changes in the immune profile of tumors following the combination therapy. Notably, the therapy reduced the presence of neutrophils—a type of immune cell associated with tumor progression and immune suppression.

“By depleting neutrophils and modulating immune responses, ketone supplementation could have broader implications for treating inflammatory diseases beyond cancer,” Murphy explained.

While further clinical studies are needed to validate these findings in human subjects, the study represents a significant step forward in understanding the potential of combining dietary interventions with immunotherapy for cancer treatment.



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