Researchers at UC San Diego’s School of Biological Sciences and School of Medicine have made a groundbreaking discovery about programmed cell death protein 1 (PD-1), a leading target in cancer treatments. The study found that PD-1 in mice is significantly weaker than the human version, revealing several previously unknown characteristics.
The researchers, led by Takeya Masubuchi, conducted comprehensive analyses, including novel biochemical tests and animal modeling. They discovered a motif—a specific sequence of amino acids—that is vastly different between rodents and humans.
“Our work uncovers unexpected species-specific features of PD-1 with implications for developing better pre-clinical models for PD-1,” said Associate Professor Enfu Hui. The study’s findings suggest that these differences can lead to functional variations in immune checkpoint receptors across species.
The researchers also tested the impact of humanizing mouse PD-1 by replacing it with the human version and found that this disrupted the ability of T cells to combat tumors. This highlights the need for a deeper understanding of how PD-1 works, particularly when developing new cancer treatments.
The study’s findings are published in Science Immunology and provide valuable insights into the evolution of PD-1 over millions of years. The researchers believe that their discovery may lead to more effective cancer treatments by better understanding human-specific differences in PD-1.
By re-examining rodent models, scientists can now develop medicines with greater accuracy, taking into account unique variations in immune receptor activities. This research underscores the importance of rigorous scientific inquiry and model system development in advancing medicine and drug discovery.
Source: https://medicalxpress.com/news/2025-01-scientists-unveil-human-mouse-differences.html