The research team led by Lin Dongxin, Zheng Jian, and Wang Liqin from the Cancer Prevention and Treatment Center of Sun Yat-sen University and the National Key Laboratory of Malignant Tumor Prevention and Treatment in South China published a research paper titled “QDPR deficiency drives immune suppression in pancreatic cancer” in the Cell Metabolism journal.
This study found that in pancreatic ductal adenocarcinoma (PDAC), quinone dihydropterin reductase (QDPR) deficiency leads to immunosuppression of pancreatic cancer. QDPR deficiency leads to resistance to immune checkpoint blockade (ICB) therapy through the biopterin metabolic pathway, and QDPR expression levels can serve as predictive biomarkers for ICB therapy in PDAC. Supplementing with BH4 can make QDPR-deficient PDAC models sensitive to ICB therapy.
Our Featured Products
| Cat.No. | Product Name | Source | Species | Tag |
| QDPR-3732H | Recombinant Human QDPR protein, GST-tagged | E.coli | Human | GST |
| QDPR-2090H | Recombinant Human QDPR, His-tagged | E.coli | Human | His |
| QDPR-160H | Recombinant Human QDPR Protein, MYC/DDK-tagged | HEK293 | Human | Myc/DDK |
| QDPR-6130H | Recombinant Human QDPR Protein (Met1-Phe244), N-His tagged | E.coli | Human | N-His |
| QDPR-13760M | Recombinant Mouse QDPR Protein | Mammalian Cell | Mouse | His |
| QDPR-7321M | Recombinant Mouse QDPR Protein, His (Fc)-Avi-tagged | HEK293 | Mouse | His (Fc)-Avi |
| CXCL1-11715H | Recombinant Human CXCL1, His-tagged | E.coli | Human | His |
| CXCL1-195H | Recombinant Human CXCL1 protein(Ala35-Asn107), His&NusA-tagged | E. coli | Human | N-His&NusA |
| CXCL1-01P | Recombinant Pan troglodytes CXCL1 Protein | E.coli | Pan troglodytes |
In the biopterin metabolism pathway, quinone dihydropteridine reductase (QDPR) mainly catalyzes the conversion of qBH2 to BH4. Existing studies have shown that QDPR can counteract the oxidation of tetrahydrofolate in tumor cells while retaining intracellular folate concentration. However, the expression pattern of QDPR in tumors, its significance for tumor prognosis, its correlation with tumor immunogenicity, and its impact on BH4/BH2 have not been elucidated.
In this study, the research team confirmed the interaction between tumor cell hijacking biopterin metabolism and tumor immunity in pancreatic ductal adenocarcinoma (PDAC) and proposed QDPR as a biomarker for ICB. Supplementing BH4 can overcome PDAC’s resistance to ICB due to QDPR deficiency.
Specifically, the study found that in PDAC, the lack of quinone dihydropterin reductase (QDPR), a key enzyme regulating biopterin metabolism, would lead to the accumulation of metabolite BH2 and reduce the ratio of BH4/BH2. The decrease in BH4/BH2 ratio leads to an increase in reactive oxygen species (ROS) generation and a decrease in H3K27me3 in the CXCL1 promoter region. Therefore, myeloid-derived inhibitory cells are recruited into the tumor microenvironment through CXCR2, leading to resistance to ICB therapy. Further research has shown that in PDAC with QDPR deficiency, supplementing with BH4 can restore the BH4/BH2 ratio, enhance anti-tumor immunity, and overcome ICB resistance. Tumors with low expression of QDPR exhibit reduced responsiveness to ICB treatment.
These findings provide new strategies for the selection and combination therapy of PDAC patients, thereby helping to improve the effectiveness of ICB treatment.
Related Products and Services
Protein Expression and Purification Services
Reference
Liu J, He X, Deng S, Zhao S, Zhang S, Chen Z, Xue C, Zeng L, Zhao H, Zhou Y, Bai R, Xu Z, Liu S, Zhou Q, Li M, Zhang J, Huang X, Chen R, Wang L, Lin D, Zheng J. QDPR deficiency drives immune suppression in pancreatic cancer. Cell Metab. 2024 Apr 15:S1550-4131(24)00119-0. doi: 10.1016/j.cmet.2024.03.015. Epub ahead of print. PMID: 38642552.