Researchers at UC San Diego have revealed notable differences in the PD-1 protein between rodents and humans, potentially challenging the reliability of rodent models used in cancer immunotherapy research. PD-1 (programmed cell death protein 1) is a critical immune checkpoint that regulates immune responses, and its role in cancer treatments has been a focus since its discovery in the 1990s. Effective PD-1 blockade has led to significant cancer therapies but is only successful in a limited number of patients. This study highlights that rodent PD-1 is weaker than its human counterpart, attributed to evolutionary changes dating back to the mass extinction event 66 million years ago. Through biochemical analysis and evolutionary mapping, researchers found distinct amino acid sequences in PD-1 that are crucial for its functionality. The findings suggest that reliance on rodent models for drug effectiveness may be misguided, as differences could influence response to therapies. The research calls for reevaluation of pre-clinical models to ensure more accurate representation of human biology in drug development. The full study is published in Science Immunology, emphasizing the need for refined approaches to understanding PD-1’s role in tumor immunology across different species.
