{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:12:41Z","timestamp":1788581561794,"version":"build-2803163510"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":57,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473071"],"award-info":[{"award-number":["82473071"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Program for Shanghai Outstanding Academic Leader (LJRC2102); National Science and Technology Major Project"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Bone metastasis is a lethal consequence of breast cancer. AT-rich interaction domain 1\u2009A gene (\n                    <jats:italic>ARID1A<\/jats:italic>\n                    ), a subunit of the switch\/sucrose non-fermentable (SWI\/SNF) complex, regulates immunosuppressive tumor microenvironment. However, its specific role in bone metastasis remains unclear. Here, we show that female patients with\n                    <jats:italic>ARID1A<\/jats:italic>\n                    \u2011mutated triple negative breast cancer (TNBC) exhibit a higher bone metastasis incidence. Most\n                    <jats:italic>ARID1A<\/jats:italic>\n                    mutations result in loss of protein expression.\n                    <jats:italic>ARID1A<\/jats:italic>\n                    deficiency upregulates the arginine metabolic pathway, increasing ornithine and spermine levels that promote the expansion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) within the bone marrow, thereby facilitating bone metastasis. Targeting key enzymes of arginase 2 (ARG2) and ornithine decarboxylase 1 (ODC1) in arginine metabolic pathway effectively reduces bone metastasis in\n                    <jats:italic>ARID1A<\/jats:italic>\n                    -deficient models. Collectively, these findings reveal that\n                    <jats:italic>ARID1A<\/jats:italic>\n                    deficiency promotes bone metastasis by activating arginine metabolism to expand PMN-MDSCs and potentially offers therapeutic strategies for preventing bone metastasis in female patients with\n                    <jats:italic>ARID1A<\/jats:italic>\n                    -deficient TNBC.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-73574-3","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:19:21Z","timestamp":1779794361000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting arginine metabolism reverses bone immunosuppressive microenvironment and metastasis in ARID1A-deficient triple negative breast cancer"],"prefix":"10.1038","volume":"17","author":[{"given":"Shuangyue","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2305-8436","authenticated-orcid":false,"given":"Boya","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangqian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aima","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenyuqi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5474-6890","authenticated-orcid":false,"given":"Mengdi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3975-3803","authenticated-orcid":false,"given":"Zhonghua","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6148-9186","authenticated-orcid":false,"given":"Xichun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"73574_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 71, 209\u2013249 (2021).","journal-title":"CA Cancer J. Clin."},{"key":"73574_CR2","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/nri3049","volume":"11","author":"A Zlotnik","year":"2011","unstructured":"Zlotnik, A., Burkhardt, A. M. & Homey, B. Homeostatic chemokine receptors and organ-specific metastasis. Nat. Rev. Immunol. 11, 597\u2013606 (2011).","journal-title":"Nat. Rev. Immunol."},{"key":"73574_CR3","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1016\/j.cell.2021.03.011","volume":"184","author":"W Zhang","year":"2021","unstructured":"Zhang, W. et al. The bone microenvironment invigorates metastatic seeds for further dissemination. Cell 184, 2471\u20132486 e2420 (2021).","journal-title":"Cell"},{"key":"73574_CR4","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1158\/2159-8290.CD-23-0543","volume":"15","author":"R Alam","year":"2025","unstructured":"Alam, R. et al. Bone-induced HER2 promotes secondary metastasis in HR+\/HER2- breast cancer. Cancer Discov. 15, 818\u2013837 (2025).","journal-title":"Cancer Discov."},{"key":"73574_CR5","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.ccell.2018.08.008","volume":"34","author":"P Razavi","year":"2018","unstructured":"Razavi, P. et al. The genomic landscape of endocrine-resistant advanced breast cancers. Cancer Cell 34, 427\u2013438 e426 (2018).","journal-title":"Cancer Cell"},{"key":"73574_CR6","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/s41588-019-0554-0","volume":"52","author":"G Xu","year":"2020","unstructured":"Xu, G. et al. ARID1A determines luminal identity and therapeutic response in estrogen-receptor-positive breast cancer. Nat. Genet 52, 198\u2013207 (2020).","journal-title":"Nat. Genet"},{"key":"73574_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19342-3","volume":"11","author":"GT Lang","year":"2020","unstructured":"Lang, G. T. et al. Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing. Nat. Commun. 11, 5679 (2020).","journal-title":"Nat. Commun."},{"key":"73574_CR8","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/s41588-019-0541-5","volume":"52","author":"S Nagarajan","year":"2020","unstructured":"Nagarajan, S. et al. ARID1A influences HDAC1\/BRD4 activity, intrinsic proliferative capacity and breast cancer treatment response. Nat. Genet 52, 187\u2013197 (2020).","journal-title":"Nat. Genet"},{"key":"73574_CR9","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1517\/14728222.2015.1062879","volume":"19","author":"BG Bitler","year":"2015","unstructured":"Bitler, B. G., Fatkhutdinov, N. & Zhang, R. Potential therapeutic targets in ARID1A-mutated cancers. Expert Opin. Ther. Targets 19, 1419\u20131422 (2015).","journal-title":"Expert Opin. Ther. Targets"},{"key":"73574_CR10","doi-asserted-by":"publisher","first-page":"3390","DOI":"10.1016\/j.cell.2024.04.025","volume":"187","author":"MB Maxwell","year":"2024","unstructured":"Maxwell, M. B. et al. ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity. Cell 187, 3390\u20133408 e3319 (2024).","journal-title":"Cell"},{"key":"73574_CR11","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/s41591-018-0012-z","volume":"24","author":"J Shen","year":"2018","unstructured":"Shen, J. et al. ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade. Nat. Med. 24, 556\u2013562 (2018).","journal-title":"Nat. Med"},{"key":"73574_CR12","doi-asserted-by":"publisher","first-page":"2712","DOI":"10.1172\/JCI134402","volume":"130","author":"J Li","year":"2020","unstructured":"Li, J. et al. Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy. J. Clin. Invest 130, 2712\u20132726 (2020).","journal-title":"J. Clin. Invest"},{"key":"73574_CR13","doi-asserted-by":"publisher","first-page":"5468","DOI":"10.1038\/s41388-021-01930-2","volume":"40","author":"J Wang","year":"2021","unstructured":"Wang, J. et al. Enhancement of E-cadherin expression and processing and driving of cancer cell metastasis by ARID1A deficiency. Oncogene 40, 5468\u20135481 (2021).","journal-title":"Oncogene"},{"key":"73574_CR14","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1158\/2159-8290.CD-20-1647","volume":"11","author":"P Aftimos","year":"2021","unstructured":"Aftimos, P. et al. Genomic and transcriptomic analyses of breast cancer primaries and matched metastases in AURORA, the Breast International Group (BIG) molecular screening initiative. Cancer Discov. 11, 2796\u20132811 (2021).","journal-title":"Cancer Discov."},{"key":"73574_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06435-w","volume":"15","author":"J Chen","year":"2024","unstructured":"Chen, J., Cui, L., Lu, S. & Xu, S. Amino acid metabolism in tumor biology and therapy. Cell Death Dis. 15, 42 (2024).","journal-title":"Cell Death Dis."},{"key":"73574_CR16","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1038\/s44318-025-00379-3","volume":"44","author":"TS Fung","year":"2025","unstructured":"Fung, T. S., Ryu, K. W. & Thompson, C. B. Arginine: at the crossroads of nitrogen metabolism. EMBO J. 44, 1275\u20131293 (2025).","journal-title":"EMBO J."},{"key":"73574_CR17","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1158\/0008-5472.CAN-21-0763","volume":"82","author":"X Liu","year":"2022","unstructured":"Liu, X. et al. Chromatin remodeling induced by ARID1A loss in lung cancer promotes glycolysis and confers JQ1 vulnerability. Cancer Res. 82, 791\u2013804 (2022).","journal-title":"Cancer Res"},{"key":"73574_CR18","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1002\/hep.30487","volume":"69","author":"A Moore","year":"2019","unstructured":"Moore, A. et al. Arid1a loss drives nonalcoholic steatohepatitis in mice through epigenetic dysregulation of hepatic lipogenesis and fatty acid oxidation. Hepatology 69, 1931\u20131945 (2019).","journal-title":"Hepatology"},{"key":"73574_CR19","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1038\/nm.3394","volume":"19","author":"DF Quail","year":"2013","unstructured":"Quail, D. F. & Joyce, J. A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19, 1423\u20131437 (2013).","journal-title":"Nat. Med"},{"key":"73574_CR20","doi-asserted-by":"publisher","first-page":"104683","DOI":"10.1016\/j.phrs.2020.104683","volume":"153","author":"KGK Deepak","year":"2020","unstructured":"Deepak, K. G. K. et al. Tumor microenvironment: challenges and opportunities in targeting metastasis of triple negative breast cancer. Pharm. Res. 153, 104683 (2020).","journal-title":"Pharm. Res"},{"key":"73574_CR21","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.immuni.2021.04.004","volume":"54","author":"S Hegde","year":"2021","unstructured":"Hegde, S., Leader, A. M. & Merad, M. MDSC: markers, development, states, and unaddressed complexity. Immunity 54, 875\u2013884 (2021).","journal-title":"Immunity"},{"key":"73574_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12150","volume":"7","author":"V Bronte","year":"2016","unstructured":"Bronte, V. et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat. Commun. 7, 12150 (2016).","journal-title":"Nat. Commun."},{"key":"73574_CR23","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.it.2016.01.004","volume":"37","author":"V Kumar","year":"2016","unstructured":"Kumar, V., Patel, S., Tcyganov, E. & Gabrilovich, D. I. The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment. Trends Immunol. 37, 208\u2013220 (2016).","journal-title":"Trends Immunol."},{"key":"73574_CR24","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41392-023-01337-3","volume":"8","author":"R Zhang","year":"2023","unstructured":"Zhang, R. et al. PMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway. Signal Transduct. Target Ther. 8, 97 (2023).","journal-title":"Signal Transduct. Target Ther."},{"key":"73574_CR25","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1038\/s41586-023-06511-9","volume":"621","author":"C Wang","year":"2023","unstructured":"Wang, C. et al. CD300ld on neutrophils is required for tumour-driven immune suppression. Nature 621, 830\u2013839 (2023).","journal-title":"Nature"},{"key":"73574_CR26","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq7019","volume":"14","author":"B Theivanthiran","year":"2022","unstructured":"Theivanthiran, B. et al. Tumor-intrinsic NLRP3-HSP70-TLR4 axis drives premetastatic niche development and hyperprogression during anti-PD-1 immunotherapy. Sci. Transl. Med. 14, eabq7019 (2022).","journal-title":"Sci. Transl. Med"},{"key":"73574_CR27","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1126\/science.1215040","volume":"335","author":"DG MacArthur","year":"2012","unstructured":"MacArthur, D. G. et al. A systematic survey of loss-of-function variants in human protein-coding genes. Science 335, 823\u2013828 (2012).","journal-title":"Science"},{"key":"73574_CR28","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","volume":"581","author":"KJ Karczewski","year":"2020","unstructured":"Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434\u2013443 (2020).","journal-title":"Nature"},{"key":"73574_CR29","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1038\/s41556-024-01478-9","volume":"26","author":"X Wang","year":"2024","unstructured":"Wang, X. et al. Lymphotoxin-beta promotes breast cancer bone metastasis colonization and osteolytic outgrowth. Nat. Cell Biol. 26, 1597\u20131612 (2024).","journal-title":"Nat. Cell Biol."},{"key":"73574_CR30","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/s41422-023-00810-6","volume":"33","author":"Q Wu","year":"2023","unstructured":"Wu, Q. et al. SCUBE2 mediates bone metastasis of luminal breast cancer by modulating immune-suppressive osteoblastic niches. Cell Res. 33, 464\u2013478 (2023).","journal-title":"Cell Res"},{"key":"73574_CR31","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi4298","volume":"10","author":"H Zhou","year":"2024","unstructured":"Zhou, H. et al. Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity. Sci. Adv. 10, eadi4298 (2024).","journal-title":"Sci. Adv."},{"key":"73574_CR32","doi-asserted-by":"publisher","first-page":"217047","DOI":"10.1016\/j.canlet.2024.217047","volume":"597","author":"S Wang","year":"2024","unstructured":"Wang, S. et al. YTHDF1 promotes the osteolytic bone metastasis of breast cancer via inducing EZH2 and CDH11 translation. Cancer Lett. 597, 217047 (2024).","journal-title":"Cancer Lett."},{"key":"73574_CR33","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1158\/1078-0432.CCR-24-3028","volume":"31","author":"CL Chiu","year":"2025","unstructured":"Chiu, C. L. et al. Targeting AXL inhibits the growth and metastasis of prostate cancer in bone. Clin. Cancer Res. 31, 1346\u20131358 (2025).","journal-title":"Clin. Cancer Res"},{"key":"73574_CR34","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1097\/CM9.0000000000001216","volume":"134","author":"JS Yang","year":"2020","unstructured":"Yang, J. S., Wang, C. C., Qiu, J. D., Ren, B. & You, L. Arginine metabolism: a potential target in pancreatic cancer therapy. Chin. Med J. (Engl.) 134, 28\u201337 (2020).","journal-title":"Chin. Med J. (Engl.)"},{"key":"73574_CR35","doi-asserted-by":"crossref","unstructured":"Matos, A., Carvalho, M., Bicho, M. & Ribeiro, R. Arginine and Arginases modulate metabolism, tumor microenvironment and prostate cancer progression. Nutrients. 13, 4503 (2021).","DOI":"10.3390\/nu13124503"},{"key":"73574_CR36","doi-asserted-by":"crossref","unstructured":"Alshetaiwi, H. et al. Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics. Sci Immunol. 5, eaay6017 (2020).","DOI":"10.1126\/sciimmunol.aay6017"},{"key":"73574_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-01968-2","volume":"23","author":"X Shi","year":"2024","unstructured":"Shi, X. et al. Bladder-cancer-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating fatty acid transporter protein 2 and down-regulating receptor-interacting protein kinase 3 in PMN-MDSCs. Mol. Cancer 23, 52 (2024).","journal-title":"Mol. Cancer"},{"key":"73574_CR38","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1136\/gutjnl-2024-333944","volume":"74","author":"Z Zhang","year":"2025","unstructured":"Zhang, Z. et al. E-twenty-six-specific sequence variant 5 (ETV5) facilitates hepatocellular carcinoma progression and metastasis through enhancing polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC)-mediated immunosuppression. Gut 74, 1137\u20131149 (2025).","journal-title":"Gut"},{"key":"73574_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17644-0","volume":"11","author":"A Buque","year":"2020","unstructured":"Buque, A. et al. Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer. Nat. Commun. 11, 3819 (2020).","journal-title":"Nat. Commun."},{"key":"73574_CR40","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1038\/s41392-023-01388-6","volume":"8","author":"G Qin","year":"2023","unstructured":"Qin, G. et al. Overcoming resistance to immunotherapy by targeting GPR84 in myeloid-derived suppressor cells. Signal Transduct. Target Ther. 8, 164 (2023).","journal-title":"Signal Transduct. Target Ther."},{"key":"73574_CR41","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1016\/j.scib.2024.12.039","volume":"70","author":"J Xia","year":"2025","unstructured":"Xia, J. et al. Tumor cell-derived N-acetyl-aspartyl-glutamate reshapes the tumor microenvironment to facilitate breast cancer metastasis. Sci. Bull. (Beijing) 70, 1126\u20131138 (2025).","journal-title":"Sci. Bull. (Beijing)"},{"key":"73574_CR42","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s00018-021-04043-x","volume":"79","author":"B Banerjee","year":"2021","unstructured":"Banerjee, B., Khrystoforova, I., Polis, B., Zvi, I. B. & Karasik, D. Acute hypoxia elevates arginase 2 and induces polyamine stress response in zebrafish via evolutionarily conserved mechanism. Cell Mol. Life Sci. 79, 41 (2021).","journal-title":"Cell Mol. Life Sci."},{"key":"73574_CR43","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/s41392-023-01662-7","volume":"8","author":"G Wolters-Eisfeld","year":"2023","unstructured":"Wolters-Eisfeld, G., Hackert, T. & Gungor, C. Unmasking metabolic dependencies in pancreatic cancer: aberrant polyamine synthesis as a promising new therapeutic target. Signal Transduct. Target Ther. 8, 410 (2023).","journal-title":"Signal Transduct. Target Ther."},{"key":"73574_CR44","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1016\/j.immuni.2024.05.025","volume":"57","author":"H Xu","year":"2024","unstructured":"Xu, H. et al. Cellular spermine targets JAK signaling to restrain cytokine-mediated autoimmunity. Immunity 57, 1796\u20131811 e1798 (2024).","journal-title":"Immunity"},{"key":"73574_CR45","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s40425-017-0308-4","volume":"5","author":"SM Steggerda","year":"2017","unstructured":"Steggerda, S. M. et al. Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment. J. Immunother. Cancer 5, 101 (2017).","journal-title":"J. Immunother. Cancer"},{"key":"73574_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46776-w","volume":"15","author":"G Bi","year":"2024","unstructured":"Bi, G. et al. Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. Nat. Commun. 15, 2461 (2024).","journal-title":"Nat. Commun."},{"key":"73574_CR47","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abn7571","volume":"14","author":"EM Grasset","year":"2022","unstructured":"Grasset, E. M. et al. Triple-negative breast cancer metastasis involves complex epithelial-mesenchymal transition dynamics and requires vimentin. Sci. Transl. Med. 14, eabn7571 (2022).","journal-title":"Sci. Transl. Med"},{"key":"73574_CR48","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.1158\/0008-5472.CAN-24-2418","volume":"85","author":"KA Khan","year":"2025","unstructured":"Khan, K. A. et al. Immunological Tolerance to Luciferase and Fluorescent Proteins Using Tol Mice Enables Development of Improved Tumor Models for Investigating Immunity and Metastasis. Cancer Res. 85, 2165\u20132178 (2025).","journal-title":"Cancer Res"},{"key":"73574_CR49","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/s41556-019-0309-2","volume":"21","author":"M Esposito","year":"2019","unstructured":"Esposito, M. et al. Bone vascular niche E-selectin induces mesenchymal-epithelial transition and Wnt activation in cancer cells to promote bone metastasis. Nat. Cell Biol. 21, 627\u2013639 (2019).","journal-title":"Nat. Cell Biol."},{"key":"73574_CR50","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1038\/s43018-024-00775-4","volume":"5","author":"KM Tharp","year":"2024","unstructured":"Tharp, K. M. et al. Tumor-associated macrophages restrict CD8(+) T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment. Nat. Cancer 5, 1045\u20131062 (2024).","journal-title":"Nat. Cancer"},{"key":"73574_CR51","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.ymthe.2022.10.013","volume":"31","author":"C Hu","year":"2023","unstructured":"Hu, C. et al. Polyamines from myeloid-derived suppressor cells promote Th17 polarization and disease progression. Mol. Ther. 31, 569\u2013584 (2023).","journal-title":"Mol. Ther."},{"key":"73574_CR52","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/nrc.2016.54","volume":"16","author":"C Engblom","year":"2016","unstructured":"Engblom, C., Pfirschke, C. & Pittet, M. J. The role of myeloid cells in cancer therapies. Nat. Rev. Cancer 16, 447\u2013462 (2016).","journal-title":"Nat. Rev. Cancer"},{"key":"73574_CR53","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/s41577-020-00490-y","volume":"21","author":"F Veglia","year":"2021","unstructured":"Veglia, F., Sanseviero, E. & Gabrilovich, D. I. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat. Rev. Immunol. 21, 485\u2013498 (2021).","journal-title":"Nat. Rev. Immunol."},{"key":"73574_CR54","doi-asserted-by":"crossref","unstructured":"Sanchez-Leon, M. L. et al. Defining the emergence of new immunotherapy approaches in breast cancer: role of myeloid-derived suppressor cells. Int. J. Mol. Sci. 24, 5208 (2023).","DOI":"10.3390\/ijms24065208"},{"key":"73574_CR55","doi-asserted-by":"crossref","unstructured":"Quail, D. F. et al. Neutrophil phenotypes and functions in cancer: a consensus statement. J Exp Med. 219, e20220011 (2022).","DOI":"10.1084\/jem.20220011"},{"key":"73574_CR56","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/s41568-020-0281-y","volume":"20","author":"S Jaillon","year":"2020","unstructured":"Jaillon, S. et al. Neutrophil diversity and plasticity in tumour progression and therapy. Nat. Rev. Cancer 20, 485\u2013503 (2020).","journal-title":"Nat. Rev. Cancer"},{"key":"73574_CR57","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/j.ccell.2025.03.015","volume":"43","author":"Y Zhu","year":"2025","unstructured":"Zhu, Y. et al. Cancer cell-derived arginine fuels polyamine biosynthesis in tumor-associated macrophages to promote immune evasion. Cancer Cell 43, 1045\u20131060 e1047 (2025).","journal-title":"Cancer Cell"},{"key":"73574_CR58","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.cell.2016.12.039","volume":"168","author":"MG Vander Heiden","year":"2017","unstructured":"Vander Heiden, M. G. & DeBerardinis, R. J. Understanding the Intersections between Metabolism and Cancer Biology. Cell 168, 657\u2013669 (2017).","journal-title":"Cell"},{"key":"73574_CR59","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0646-3","volume":"16","author":"X Luo","year":"2017","unstructured":"Luo, X. et al. Emerging roles of lipid metabolism in cancer metastasis. Mol. Cancer 16, 76 (2017).","journal-title":"Mol. Cancer"},{"key":"73574_CR60","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/j.cmet.2023.07.006","volume":"35","author":"Y Xiao","year":"2023","unstructured":"Xiao, Y. et al. Emerging therapies in cancer metabolism. Cell Metab. 35, 1283\u20131303 (2023).","journal-title":"Cell Metab."},{"key":"73574_CR61","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41573-021-00339-6","volume":"21","author":"ZE Stine","year":"2022","unstructured":"Stine, Z. E., Schug, Z. T., Salvino, J. M. & Dang, C. V. Targeting cancer metabolism in the era of precision oncology. Nat. Rev. Drug Discov. 21, 141\u2013162 (2022).","journal-title":"Nat. Rev. Drug Discov."},{"key":"73574_CR62","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.ccell.2014.11.017","volume":"27","author":"H Wang","year":"2015","unstructured":"Wang, H. et al. The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells. Cancer Cell 27, 193\u2013210 (2015).","journal-title":"Cancer Cell"},{"key":"73574_CR63","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1038\/ncb3613","volume":"19","author":"X Zhuang","year":"2017","unstructured":"Zhuang, X. et al. Differential effects on lung and bone metastasis of breast cancer by Wnt signalling inhibitor DKK1. Nat. Cell Biol. 19, 1274\u20131285 (2017).","journal-title":"Nat. Cell Biol."},{"key":"73574_CR64","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.4049\/jimmunol.1000901","volume":"185","author":"MG Lechner","year":"2010","unstructured":"Lechner, M. G., Liebertz, D. J. & Epstein, A. L. Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J. Immunol. 185, 2273\u20132284 (2010).","journal-title":"J. Immunol."},{"key":"73574_CR65","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.cmet.2022.11.013","volume":"35","author":"HN Bell","year":"2023","unstructured":"Bell, H. N. et al. Microenvironmental ammonia enhances T cell exhaustion in colorectal cancer. Cell Metab. 35, 134\u2013149 e136 (2023).","journal-title":"Cell Metab."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73574-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73574-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73574-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T23:02:14Z","timestamp":1784674934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73574-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["73574"],"URL":"https:\/\/doi.org\/10.1038\/s41467-026-73574-3","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]},"assertion":[{"value":"13 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"6863"}}