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Title: New Metabolic Target Identified for Enhancing Cancer Immunotherapy

Germany, 2nd Jul 2024 - Cancer remains one of the most challenging diseases to treat, with many patients not responding as anticipated to existing therapies. However, the benefits of immunotherapy have opened new avenues for treatment by targeting cancer cell metabolism. Researchers at the VIB-KU Leuven Center for Cancer Biology have identified the CDA gene as a potential metabolic target in immunotherapy-resistant pancreatic ductal adenocarcinoma (PDAC). Led by Professor Massimiliano Mazzone, the study, published in Nature Cancer, reveals promising new avenues for enhancing the effectiveness of cancer treatments.CDA Gene and Immunotherapy ResistanceThe CDA gene, which codes for the enzyme cytidine deaminase, plays a crucial role in recycling parts of DNA and RNA and inactivating certain cancer drugs. While previous research has linked CDA to chemotherapy resistance, its role in immunotherapy resistance is less explored. This new study is novel in focusing on CDA’s role in PDAC immunotherapy resistance, providing fresh insights into overcoming this challenge.Mechanism of CDA InhibitionThe study’s analysis of PDAC tumor datasets—both responsive and resistant to immune checkpoint blockade (ICB)—revealed that high CDA levels lead to the production of uridine-diphosphate (UDP). This molecule interacts with tumor-associated macrophages (TAMs), which comprise about 50% of tumor mass and are associated with tumor progression. UDP promotes an immunosuppressive phenotype in TAMs, aiding the tumor’s evasion of immune attacks.By inhibiting CDA through genetic or pharmacological means, the researchers observed better T-cell infiltration into the tumors and increased susceptibility to immunotherapy. This suggests that targeting CDA or the UDP receptor in TAMs can significantly...

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