{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cheng H"],"funding":["Outstanding Youth Foundation of Jiangsu Province of China","National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["314-330"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9970874"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(2)"],"pubmed_abstract":["The accumulation of acidic metabolic waste products within the tumor microenvironment inhibits effector functions of tumor-infiltrating lymphocytes (TILs). However, it remains unclear how an acidic environment affects T cell metabolism and differentiation. Here we show that prolonged exposure to acid reprograms T cell intracellular metabolism and mitochondrial fitness and preserves T cell stemness. Mechanistically, elevated extracellular acidosis impairs methionine uptake and metabolism via downregulation of SLC7A5, therefore altering H3K27me3 deposition at the promoters of key T cell stemness genes. These changes promote the maintenance of a 'stem-like memory' state and improve long-term in vivo persistence and anti-tumor efficacy in mice. Our findings not only reveal an unexpected capacity of extracellular acidosis to maintain the stem-like properties of T cells, but also advance our understanding of how methionine metabolism affects T cell stemness."],"journal":["Nature metabolism"],"pubmed_title":["Extracellular acidosis restricts one-carbon metabolism and preserves T cell stemness."],"pmcid":["PMC9970874"],"funding_grant_id":["BK20211505","BK20220049","81972875","81971466"],"pubmed_authors":["Pan X","Li G","Tao M","Chen L","Zhang L","Frankiw L","Qiu Y","Xie E","Yin H","Ma K","Du J","Zhu W","Cheng H","Wang Z","Xu Y"],"additional_accession":[]},"is_claimable":false,"name":"Extracellular acidosis restricts one-carbon metabolism and preserves T cell stemness.","description":"The accumulation of acidic metabolic waste products within the tumor microenvironment inhibits effector functions of tumor-infiltrating lymphocytes (TILs). However, it remains unclear how an acidic environment affects T cell metabolism and differentiation. Here we show that prolonged exposure to acid reprograms T cell intracellular metabolism and mitochondrial fitness and preserves T cell stemness. Mechanistically, elevated extracellular acidosis impairs methionine uptake and metabolism via downregulation of SLC7A5, therefore altering H3K27me3 deposition at the promoters of key T cell stemness genes. These changes promote the maintenance of a 'stem-like memory' state and improve long-term in vivo persistence and anti-tumor efficacy in mice. Our findings not only reveal an unexpected capacity of extracellular acidosis to maintain the stem-like properties of T cells, but also advance our understanding of how methionine metabolism affects T cell stemness.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2025-04-26T10:19:36.043Z","creation":"2025-04-06T13:17:58.042Z"},"accession":"S-EPMC9970874","cross_references":{"pubmed":["36717749"],"doi":["10.1038/s42255-022-00730-6"]}}