A protein that fuels cancer could also be the key to fighting it
Scientists have discovered how to turn a protein that normally fuels cancer growth into a weapon against it. By activating PPARD in immune cells, researchers made them better at burning fat and attacking tumors, slowing or stopping cancer growth in laboratory experiments. The approach showed promise against colorectal, breast, and ovarian cancers, as well as melanoma.
Key points
- Scientists at Cold Spring Harbor Laboratory found that activating the protein PPARD in immune cells can make them attack tumors more effectively.
- PPARD-activated CAR T cells slowed or stopped tumor growth in experimental models of human colorectal cancer, and promising results also appeared in breast cancer, ovarian cancer and melanoma.
- The approach has not yet been proven in patients, and the laboratory is now investigating whether it could also help treat endometriosis.
Scientists at Cold Spring Harbor Laboratory (CSHL) have found that a protein which helps cancer grow may also be able to help fight it. The research, published in Nature Immunology, shows that activating this protein in immune cells can make them more effective at attacking tumors.
The work centers on peroxisome proliferator-activated receptor delta (PPARD), a transcription factor that helps regulate how cells burn fat for energy. The findings could matter most for colorectal cancer, which the article says has become the leading cause of cancer-related death among people under 50.
How the experiments worked
Beyaz and his colleagues first studied mice with colorectal cancer. They found that while cancer cells use PPARD to support their own activity, activating the same protein in immune cells shifted the surrounding environment toward one that favored the immune system's attack on cancer.
The team then activated PPARD in engineered immune cells known as CAR T cells, which are modified to recognize and attack cancer. They tested these cells against several experimental models of human colorectal cancer, including organoids grown from patient tissue and human cancer cells cultured in dishes and implanted into mice. The PPARD-activated CAR T cells slowed or stopped tumor growth, though the article notes the approach has not yet been proven in patients.
It's the classic fight between good and evil. How can good ultimately prevail? Activating PPARD in immune cells could be the way.
— Semir Beyaz
Results in other cancers
Colorectal cancer was the initial focus, but the team also confirmed promising results in breast cancer, ovarian cancer and melanoma. The article says this raises the possibility that improving immune cell fitness could become a broader strategy for tumors that are hard to control with current therapies.
Beyaz said the discoveries are only the "tip of the iceberg" for strengthening cancer immunotherapy. He added that boosting immune cell fitness may also help with other conditions where the immune system fails to clear diseased cells, and his laboratory is now investigating endometriosis, which affects approximately one in 10 women.
