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However, the extent to which the PCNSL TME shapes the metabolic and functional states of tumor and non\u2010tumor microenvironment cells remains largely unexplored. Utilizing single\u2010cell\u00a0multi\u2010omic\u00a0approaches, we systematically dissected tumor\u2010TME interactions in PCNSL and showed that glucose deprivation within the TME leads to enhanced\n                    <jats:italic>SLC2A5<\/jats:italic>\n                    \u2010mediated fructose metabolism in tumor cells and contributes to T cell dysfunction. Furthermore, hypoxia within the TME induces\n                    <jats:italic>SLC2A5<\/jats:italic>\n                    expression in tumor\u2010supportive macrophages through HIF\u2010dependent transcriptional regulation, establishing\n                    <jats:italic>SLC2A5<\/jats:italic>\n                    and its associated fructose metabolism as potential metabolic vulnerabilities in both tumor cells and tumor\u2010supportive macrophages. In vitro and in vivo functional assays further demonstrated that genetic and pharmacologic inhibition of\n                    <jats:italic>SLC2A5<\/jats:italic>\n                    \u2010mediated fructose uptake markedly suppressed lymphoma growth. Collectively, our study uncovers a novel potential metabolic liability targeting tumor\u2013TME interactions in PCNSL.\n                  <\/jats:p>","DOI":"10.1002\/advs.76316","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:15:16Z","timestamp":1782476116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Cell Profiling Identifies\n                    <i>SLC2A5<\/i>\n                    \u2010Mediated Fructose Metabolism as a Vulnerability in Primary CNS Lymphoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Qiaoli","family":"Wu","sequence":"first","affiliation":[{"name":"Huanhu Hospital Affiliated to Tianjin Medical University Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Cerebral Blood Flow Reconstruction and Head and Neck Tumor New Technology Translation Tianjin Neurosurgical Institute Tianjin Huanhu Hospital  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