Cancer-linked protein PPARD may help immune cells attack tumors
Researchers at Cold Spring Harbor Laboratory discovered that switching on PPARD in immune cells enhanced their ability to burn fat and attack tumors in laboratory experiments. The strategy reduced or halted cancer growth in models of colorectal, breast, and ovarian cancers, as well as melanoma. The results point to a possible way to turn a cancer-associated protein into an immunotherapy tool.
The protein at issue, PPARD, is a transcription factor that governs how cells metabolize fat for energy. At Cold Spring Harbor Laboratory, Semir Beyaz's team proposed that the metabolic traits enabling cancer cells to thrive might overlap with those that make immune cells effective. In mouse colorectal cancer models, switching on PPARD in immune cells reshaped the tumor surroundings in the immune system's favor.
The group then engineered CAR T cells, which are immune cells already modified to target cancer in some existing therapies, to activate PPARD. Tested against patient-derived organoids, cultured human cancer cells, and mouse implants, these cells curbed tumor growth. The work appeared in Nature Immunology and has not yet been tested in patients.
If the approach holds up in people, it could matter most for patients facing hard-to-treat colorectal cancer, now a leading cause of cancer death in adults under 50, along with those with breast, ovarian, or skin cancers. Because it repurposes an existing immunotherapy platform rather than introducing a wholly new one, it may be easier to test in trials. Still, laboratory success often fails to translate, so any clinical benefit remains uncertain and years away.