Ji Liu, Xiaowei He, Shuang Deng, Sihan Zhao, Shaoping Zhang, Ziming Chen, Chunling Xue, Lingxing Zeng, Hongzhe Zhao, Yifan Zhou, Ruihong Bai, Zilan Xu, Shaoqiu Liu, Quanbo Zhou, Mei Li, Jialiang Zhang, Xudong Huang, Rufu Chen, Liqin Wang, Dongxin Lin, Jian Zheng
The relevance of biopterin metabolism in resistance to immune checkpoint blockade (ICB) therapy remains unknown. We demonstrate that the deficiency of quinoid dihydropteridine reductase (QDPR), a critical enzyme regulating biopterin metabolism, causes metabolite dihydrobiopterin (BH2) accumulation and decreases the ratio of tetrahydrobiopterin (BH4) to BH2 in pancreatic ductal adenocarcinomas (PDACs). The reduced BH4/BH2 ratio leads to an increase in reactive oxygen species (ROS) generation and a decrease in the distribution of H3K27me3 at CXCL1 promoter...
April 15, 2024: Cell Metabolism