{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xu X"],"funding":["NIDDK NIH HHS","NCI NIH HHS","NIH HHS"],"pagination":["932-943.e8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12118570"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(5)"],"pubmed_abstract":["Nucleotides perform important metabolic functions, carrying energy and feeding nucleic acid synthesis. Here, we use isotope tracing-mass spectrometry to quantitate contributions to purine nucleotides from salvage versus de novo synthesis. We further explore the impact of augmenting a key precursor for purine synthesis, one-carbon (1C) units. We show that tumors and tumor-infiltrating T cells (relative to splenic or lymph node T cells) synthesize purines de novo. Shortage of 1C units for T cell purine synthesis is accordingly a potential bottleneck for anti-tumor immunity. Supplementing 1C units by infusing formate drives formate assimilation into purines in tumor-infiltrating T cells. Orally administered methanol functions as a formate pro-drug, with deuteration enabling kinetic control of"],"journal":["Cell chemical biology"],"pubmed_title":["One-carbon unit supplementation fuels purine synthesis in tumor-infiltrating T cells and augments checkpoint blockade."],"pmcid":["PMC12118570"],"funding_grant_id":["S10 OD028592","DP1 DK113643","R01 CA163591"],"pubmed_authors":["Rabinowitz JD","Chen Z","Xing X","Bartman CR","Xu X","Olszewski K"],"additional_accession":[]},"is_claimable":false,"name":"One-carbon unit supplementation fuels purine synthesis in tumor-infiltrating T cells and augments checkpoint blockade.","description":"Nucleotides perform important metabolic functions, carrying energy and feeding nucleic acid synthesis. Here, we use isotope tracing-mass spectrometry to quantitate contributions to purine nucleotides from salvage versus de novo synthesis. We further explore the impact of augmenting a key precursor for purine synthesis, one-carbon (1C) units. We show that tumors and tumor-infiltrating T cells (relative to splenic or lymph node T cells) synthesize purines de novo. Shortage of 1C units for T cell purine synthesis is accordingly a potential bottleneck for anti-tumor immunity. Supplementing 1C units by infusing formate drives formate assimilation into purines in tumor-infiltrating T cells. Orally administered methanol functions as a formate pro-drug, with deuteration enabling kinetic control of","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-05-29T17:15:19.084Z","creation":"2026-04-08T05:26:06.58Z"},"accession":"S-EPMC12118570","cross_references":{"pubmed":["38759619"],"doi":["10.1016/j.chembiol.2024.04.007"]}}