keto diet plus immunotherapy may reduce prostate cancer
The webinar discusses recent breakthroughs in cancer immunotherapy, which involves harnessing the body's own immune system to fight cancer. The immune system is usually very good at attacking foreign invaders like viruses, but has a harder time recognizing and attacking cancer cells.
Dr. Allison and his colleagues discovered that there are "brakes" on immune cells called checkpoints that normally prevent them from attacking the body's own healthy cells. Tumor cells often take advantage of these checkpoints to evade attack by immune cells.
Dr. Allison developed antibody drugs that release these brakes, allowing immune cells to vigorously attack tumors. In clinical trials, these checkpoint inhibitor drugs have produced very long-lasting responses in some patients with advanced cancers like melanoma.
Dr. Freeman discovered another important checkpoint called PD-1. Drugs targeting PD-1 have also shown great promise against a variety of cancer types. However, many patients still do not respond to checkpoint inhibitors.
The researchers believe the key to extending these therapies to more patients is to find ways to better activate the immune response against tumors and combine checkpoint inhibitors with other treatments. For cancers with few mutations, it may be necessary to find ways to drive immune cells into the tumor.
Releasing multiple checkpoints, enhancing immune cell activation, and combining checkpoint drugs with targeted therapies, radiation, or other approaches could make immunotherapy effective for many more cancer patients. While there are still challenges ahead, cancer immunotherapy has emerged as a very promising approach that is saving the lives of many patients.
Component of keto diet plus immunotherapy may reduce prostate cancer | ScienceDaily
Adding a pre-ketone supplement -- a component of a high-fat, low-carb ketogenic diet -- to a type of cancer therapy in a laboratory setting was highly effective for treating prostate cancer, researchers from the University of Notre Dame found.
Recently published online in the journal Cancer Research, the study from Xin Lu, the John M. and Mary Jo Boler Collegiate Associate Professor in the Department of Biological Sciences, and collaborators tackled a problem oncologists have battled: Prostate cancer is resistant to a type of immunotherapy called immune checkpoint blockade (ICB) therapy. ICB therapy blocks certain proteins from binding with other proteins and paves the way for our body's fighter cells, T cells, to kill the cancer.
"Prostate cancer is the most common cancer for American men, and immunotherapy has been really influential in some other cancers, like melanoma or lung cancer, but it hasn't been working almost at all for prostate cancer," said Lu, who is affiliated with the Boler-Parseghian Center for Rare and Neglected Diseases. Adding a dietary supplement might overcome this resistance, the lead author in the study, Sean Murphy, suggested.
Murphy, a '24 alumnus who was a doctoral student in Lu's lab, had been following a keto diet himself. Knowing that cancer cells feed off of sugar, he decided that depriving mouse models of carbohydrates -- a key component of the keto diet -- might prevent cancer growth.
He divided the models into different groups: immunotherapy alone, ketogenic diet alone, a pre-ketone supplement alone, the ketogenic diet with the immunotherapy, the supplement with the immunotherapy, and the control. While the immunotherapy alone had almost no effect on the tumors (just like what happens to most patients with prostate cancer), both the ketogenic diet with the immunotherapy and the pre-ketone supplement with the immunotherapy reduced the cancer and extended the lives of the mouse models.
The supplement with the immunotherapy worked best.
"It turned out this combination worked really well," Lu said. "It made the tumor become very sensitive to the immunotherapy, with 23 percent of the mice cured -- they were tumor-free; in the rest, the tumors were shrinking really dramatically."
The evidence points to the possibility that a supplement providing ketones, which are what is produced in the body when people eat a keto diet, might prevent the prostate cancer cells from being resistant to immunotherapy. This may lead to future clinical studies that examine how ketogenic diets or keto supplements could enhance cancer therapy.
While keto diets allow for minimal carbohydrates, the success of this study is not about the lack of carbohydrates, Murphy and Lu stressed. It is about the presence of the ketone body, a substance produced by the liver and used as an energy source when glucose is not available. The ketones disrupt the cycle of the cancer cells, allowing the T cells to do their job to destroy them.
The discovery was also exciting on a molecular level, Lu said. Any type of dietary study can suffer from the potential issue of causation: Are the results from the diet or other changes made because of the diet? But Lu and his collaborators confirmed their results using single-cell RNA sequencing, which examines the gene expression of single cells within the tumor.
"We found that this combination of the supplement and the immunotherapy reprogrammed the whole immune profile of the tumors and recruited many T cells into the tumors to kill prostate cancer cells," Lu said.
The successful therapy also reduced the number of a type of immune cell called neutrophils. Once in the tumor microenvironment, neutrophils' natural properties become greatly distorted, and they become largely responsible for inhibiting T cell activities and allowing more tumor progression. Dysregulation of neutrophils is also associated with many other diseases.
"With the main ketone body depleting neutrophils, it opens the door for investigating the effects of the keto diet and the ketone supplement on diseases ranging from inflammatory bowel disease to arthritis," Murphy said.
Lu agreed.
"What's exciting is that we're getting closer to the mechanism, backed up by genetic models and what we're seeing in the tumors themselves, of why this works," he said.
Keto supplement may improve immunotherapy for prostate cancer - Futurity
Adding a pre-ketone supplement, a component of a high-fat, low-carb ketogenic diet, to a type of cancer therapy in a laboratory setting was highly effective for treating prostate cancer, researchers report.
As reported in the journal Cancer Research, the researchers tackled a problem oncologists have battled: Prostate cancer is resistant to a type of immunotherapy called immune checkpoint blockade (ICB) therapy. ICB therapy blocks certain proteins from binding with other proteins and paves the way for our body’s fighter cells, T cells, to kill the cancer.
“Prostate cancer is the most common cancer for American men, and immunotherapy has been really influential in some other cancers, like melanoma or lung cancer, but it hasn’t been working almost at all for prostate cancer,” says Xin Lu, associate professor in the biological sciences department at the University of Notre Dame, who is affiliated with the Boler-Parseghian Center for Rare and Neglected Diseases.
Adding a dietary supplement might overcome this resistance, suggests lead author Sean Murphy, a 2024 alumnus who was a doctoral student in Lu’s lab and had been following a keto diet himself.
Knowing that cancer cells feed off of sugar, he decided that depriving mouse models of carbohydrates—a key component of the keto diet—might prevent cancer growth.
He divided the models into different groups: immunotherapy alone, ketogenic diet alone, a pre-ketone supplement alone, the ketogenic diet with the immunotherapy, the supplement with the immunotherapy, and the control.
While the immunotherapy alone had almost no effect on the tumors (just like what happens to most patients with prostate cancer), both the ketogenic diet with the immunotherapy and the pre-ketone supplement with the immunotherapy reduced the cancer and extended the lives of the mouse models.
The supplement with the immunotherapy worked best.
“It turned out this combination worked really well,” Lu says. “It made the tumor become very sensitive to the immunotherapy, with 23% of the mice cured—they were tumor-free; in the rest, the tumors were shrinking really dramatically.”
The evidence points to the possibility that a supplement providing ketones, which are what is produced in the body when people eat a keto diet, might prevent the prostate cancer cells from being resistant to immunotherapy. This may lead to future clinical studies that examine how ketogenic diets or keto supplements could enhance cancer therapy.
While keto diets allow for minimal carbohydrates, the success of this study is not about the lack of carbohydrates, Murphy and Lu stress. It is about the presence of the ketone body, a substance produced by the liver and used as an energy source when glucose is not available. The ketones disrupt the cycle of the cancer cells, allowing the T cells to do their job to destroy them.
The discovery was also exciting on a molecular level, Lu says. Any type of dietary study can suffer from the potential issue of causation: Are the results from the diet or other changes made because of the diet? But Lu and his collaborators confirmed their results using single-cell RNA sequencing, which examines the gene expression of single cells within the tumor.
“We found that this combination of the supplement and the immunotherapy reprogrammed the whole immune profile of the tumors and recruited many T cells into the tumors to kill prostate cancer cells,” Lu says.
The successful therapy also reduced the number of a type of immune cell called neutrophils. Once in the tumor microenvironment, neutrophils’ natural properties become greatly distorted, and they become largely responsible for inhibiting T cell activities and allowing more tumor progression. Dysregulation of neutrophils is also associated with many other diseases.
“With the main ketone body depleting neutrophils, it opens the door for investigating the effects of the keto diet and the ketone supplement on diseases ranging from inflammatory bowel disease to arthritis,” Murphy says.
Lu agrees.
“What’s exciting is that we’re getting closer to the mechanism, backed up by genetic models and what we’re seeing in the tumors themselves, of why this works,” he says.
The American Institute for Cancer Research, the National Institutes of Health and a core facility grant from Indiana Clinical and Translational Sciences Institute funded the work. Other support included the Department of Defense and the Boler Family Foundation at the University of Notre Dame. A provisional patent application has been filed based on this study by the IDEA Center at Notre Dame.
Source: Deanna Csomo Ferrell for University of Notre Dame
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