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Therefore, improved therapies are urgently required to improve patient outcomes. In this study, metabolic inhibitor drug screening reveals that quinacrine elicits excellent antitumor activity both in vitro and in vivo by downregulating intracellular arginine levels in PTCL. Single\u2010cell transcriptomic analyses reveal aberrant arginine metabolism in patients with PTCL, characterized by excessive solute carrier family 3 member 2 (SLC3A2) mediated arginine uptake preferentially in tumor cells. High SLC3A2 expression predicts poor outcomes in PTCL, as SLC3A2\u2010mediated arginine uptake promotes the malignant behaviors of tumor cells and induces tumor immune escape, thereby fueling tumor progression. Mechanistically, high arginine levels induce global metabolic changes, including enhanced oxidative phosphorylation by promoting nascent RNA synthesis. This work identifies structure\u2010specific recognition protein 1 (SSRP1), which upregulates SLC3A2, as a co\u2010transcription factor with JUNB. Quinacrine disrupts SLC3A2\u2010mediated arginine transport by targeting SSRP1. Combining quinacrine with histone deacetylase inhibitors is a promising therapeutic strategy for PTCL.<\/jats:p>","DOI":"10.1002\/advs.202415698","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T02:27:12Z","timestamp":1746757632000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["SSRP1\/SLC3A2 Axis in Arginine Transport: A New Target for Overcoming Immune Evasion and Tumor Progression in Peripheral T\u2010Cell Lymphoma"],"prefix":"10.1002","volume":"12","author":[{"given":"Yimin","family":"Ren","sequence":"first","affiliation":[{"name":"Lymphoma Center, Department of Hematology, The First Affiliated Hospital with Nanjing Medical University Jiangsu Province Hospital  Nanjing 210029 China"},{"name":"Key Laboratory of Hematology of Nanjing Medical University  Nanjing 210029 China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation 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