{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T01:38:32Z","timestamp":1776735512911,"version":"3.51.2"},"reference-count":104,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":44,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273202"],"award-info":[{"award-number":["82273202"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Precis. Onc."],"DOI":"10.1038\/s41698-026-01362-9","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:53:57Z","timestamp":1772931237000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting erythroid progenitor cell metabolism to enhance cancer immunotherapy"],"prefix":"10.1038","volume":"10","author":[{"given":"Zi-Zhan","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai-Liang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Cheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Da","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Jun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"1362_CR1","first-page":"10","volume":"1","author":"RL Siegel","year":"2025","unstructured":"Siegel, R. L., Kratzer, T. B., Giaquinto, A. N., Sung, H. & Jemal, A. Cancer statistics, 2025. CA Cancer J. Clin. 1, 10\u201345 (2025).","journal-title":"CA Cancer J. Clin."},{"key":"1362_CR2","first-page":"203","volume":"3","author":"H Zeng","year":"2024","unstructured":"Zeng, H. et al. Cancer survival statistics in China 2019-2021: a multicenter, population-based study. J. Natl. Cancer Cent. 3, 203\u2013213 (2024).","journal-title":"J. Natl. Cancer Cent."},{"key":"1362_CR3","doi-asserted-by":"crossref","unstructured":"Saka, A. H. et al. Cancer statistics for African American and black people, 2025. CA Cancer J. Clin. 2, 111\u2013140 (2025).","DOI":"10.3322\/caac.21874"},{"key":"1362_CR4","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s41573-018-0006-z","volume":"3","author":"RS Riley","year":"2019","unstructured":"Riley, R. S., June, C. H., Langer, R. & Mitchell, M. J. Delivery technologies for cancer immunotherapy. Nat. Rev. Drug Discov. 3, 175\u2013196 (2019).","journal-title":"Nat. Rev. Drug Discov."},{"key":"1362_CR5","doi-asserted-by":"crossref","unstructured":"Mc Neil, V. & Lee, S. W. Advancing cancer treatment: A review of immune checkpoint inhibitors and combination strategies. Cancers (Basel) 17, 1408 (2025).","DOI":"10.3390\/cancers17091408"},{"key":"1362_CR6","doi-asserted-by":"crossref","unstructured":"Garner, H. & de Visser, K. E. Immune crosstalk in cancer progression and metastatic spread: A complex conversation. Nat. Rev. Immunol. 8, 483\u2013497 (2020).","DOI":"10.1038\/s41577-019-0271-z"},{"key":"1362_CR7","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.cell.2022.01.008","volume":"185","author":"G Morad","year":"2022","unstructured":"Morad, G., Helmink, B. A., Sharma, P. & Wargo, J. A. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell 185, 576 (2022).","journal-title":"Cell"},{"key":"1362_CR8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41577-019-0218-4","volume":"20","author":"A Kalbasi","year":"2020","unstructured":"Kalbasi, A. & Ribas, A. Tumour-intrinsic resistance to immune checkpoint blockade. Nat. Rev. Immunol. 20, 25\u201339 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"1362_CR9","doi-asserted-by":"crossref","unstructured":"Cao, L. M. et al. Extracellular vesicles: Hermes between cancers and lymph nodes. Cancer Lett. 623, 217735 (2025).","DOI":"10.1016\/j.canlet.2025.217735"},{"key":"1362_CR10","doi-asserted-by":"crossref","unstructured":"Bader, J. E., Voss, K. & Rathmell, J. C. Targeting metabolism to improve the tumor microenvironment for cancer immunotherapy. Mol. Cell 6, 1019\u20131033 (2020).","DOI":"10.1016\/j.molcel.2020.05.034"},{"key":"1362_CR11","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/bs.ircmb.2023.03.007","volume":"378","author":"ZZ Li","year":"2023","unstructured":"Li, Z. Z., He, J. Y., Wu, Q., Liu, B. & Bu, L. L. Recent advances in targeting myeloid-derived suppressor cells and their applications to radiotherapy. Int Rev. Cell Mol. Biol. 378, 233\u2013264 (2023).","journal-title":"Int Rev. Cell Mol. Biol."},{"key":"1362_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2024.189209","volume":"1879","author":"WT Mo","year":"2024","unstructured":"Mo, W. T., Huang, C. F. & Sun, Z. J. Erythroid progenitor cell modulates cancer immunity: Insights and implications. Biochim Biophys. Acta Rev. Cancer 1879, 189209 (2024).","journal-title":"Biochim Biophys. Acta Rev. Cancer"},{"key":"1362_CR13","doi-asserted-by":"publisher","first-page":"e006595","DOI":"10.1136\/jitc-2022-006595","volume":"11","author":"N Bozorgmehr","year":"2023","unstructured":"Bozorgmehr, N. et al. CD71(+) erythroid cells suppress T-cell effector functions and predict immunotherapy outcomes in patients with virus-associated solid tumors. J. Immunother. Cancer 11, e006595 (2023).","journal-title":"J. Immunother. Cancer"},{"key":"1362_CR14","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1002\/ijc.35102","volume":"11","author":"SR Li","year":"2024","unstructured":"Li, S. R., Wu, Z. Z., Yu, H. J. & Sun, Z. J. Targeting erythroid progenitor cells for cancer immunotherapy. Int J. Cancer 11, 1928\u20131938 (2024).","journal-title":"Int J. Cancer"},{"key":"1362_CR15","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/s41571-023-00846-y","volume":"2","author":"SA Lasser","year":"2024","unstructured":"Lasser, S. A., Ozbay Kurt, F. G., Arkhypov, I., Utikal, J. & Umansky, V. Myeloid-derived suppressor cells in cancer and cancer therapy. Nat. Rev. Clin. Oncol. 2, 147\u2013164 (2024).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"1362_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02208-3","volume":"24","author":"S He","year":"2025","unstructured":"He, S., Zheng, L. & Qi, C. Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy. Mol. Cancer 24, 5 (2025).","journal-title":"Mol. Cancer"},{"key":"1362_CR17","doi-asserted-by":"crossref","unstructured":"Raskov, H., Orhan, A., Gaggar, S. & Gogenur, I. Neutrophils and polymorphonuclear myeloid-derived suppressor cells: An emerging battleground in cancer therapy. Oncogenesis 11, 22 (2022).","DOI":"10.1038\/s41389-022-00398-3"},{"key":"1362_CR18","first-page":"992","volume":"4","author":"H Tang","year":"2021","unstructured":"Tang, H., Li, H. & Sun, Z. Targeting myeloid-derived suppressor cells for cancer therapy. Cancer Biol. Med 4, 992\u20131009 (2021).","journal-title":"Cancer Biol. Med"},{"key":"1362_CR19","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1038\/s41591-018-0205-5","volume":"10","author":"L Zhao","year":"2018","unstructured":"Zhao, L. et al. Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells. Nat. Med 10, 1536\u20131544 (2018).","journal-title":"Nat. Med"},{"key":"1362_CR20","doi-asserted-by":"crossref","unstructured":"Han, Y. et al. Tumor-induced generation of splenic erythroblast-like Ter-cells promotes tumor progression. Cell 184, 1392 (2021).","DOI":"10.1016\/j.cell.2020.02.036"},{"key":"1362_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216193","volume":"563","author":"YY Wang","year":"2023","unstructured":"Wang, Y. Y., Wu, Z. Z., Huang, C. F. & Sun, Z. J. Tumor-host colluding through erythroid progenitor cells: Mechanisms and opportunities. Cancer Lett. 563, 216193 (2023).","journal-title":"Cancer Lett."},{"key":"1362_CR22","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.canlet.2020.12.003","volume":"499","author":"J Chen","year":"2021","unstructured":"Chen, J. et al. Intratumoral CD45(+)CD71(+) erythroid cells induce immune tolerance and predict tumor recurrence in hepatocellular carcinoma. Cancer Lett. 499, 85\u201398 (2021).","journal-title":"Cancer Lett."},{"key":"1362_CR23","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.ccell.2022.04.018","volume":"40","author":"H Long","year":"2022","unstructured":"Long, H. et al. Tumor-induced erythroid precursor-differentiated myeloid cells mediate immunosuppression and curtail anti-PD-1\/PD-L1 treatment efficacy. Cancer Cell 40, 674\u2013693 e7 (2022).","journal-title":"Cancer Cell"},{"key":"1362_CR24","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13045-023-01473-x","volume":"16","author":"X Cheng","year":"2023","unstructured":"Cheng, X., Wang, H., Wang, Z., Zhu, B. & Long, H. Tumor-associated myeloid cells in cancer immunotherapy. J. Hematol. Oncol. 16, 71 (2023).","journal-title":"J. Hematol. Oncol."},{"key":"1362_CR25","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1515\/biol-2022-0102","volume":"1","author":"H Zhang","year":"2022","unstructured":"Zhang, H., Wan, G. Z., Wang, Y. Y., Chen, W. & Guan, J. Z. The role of erythrocytes and erythroid progenitor cells in tumors. Open Life Sci. 1, 1641\u20131656 (2022).","journal-title":"Open Life Sci."},{"key":"1362_CR26","doi-asserted-by":"publisher","first-page":"2373","DOI":"10.1002\/jcp.27262","volume":"3","author":"M Jafari","year":"2019","unstructured":"Jafari, M., Ghadami, E., Dadkhah, T. & Akhavan-Niaki, H. PI3k\/AKT signaling pathway: Erythropoiesis and beyond. J. Cell Physiol. 3, 2373\u20132385 (2019).","journal-title":"J. Cell Physiol."},{"key":"1362_CR27","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1073\/pnas.94.5.1806","volume":"5","author":"H Wu","year":"1997","unstructured":"Wu, H., Klingmuller, U., Acurio, A., Hsiao, J. G. & Lodish, H. F. Functional interaction of erythropoietin and stem cell factor receptors is essential for erythroid colony formation. Proc. Natl. Acad. Sci. USA 5, 1806\u20131810 (1997).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1362_CR28","first-page":"100","volume":"1","author":"Y Xue","year":"2011","unstructured":"Xue, Y. et al. PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells. Nat. Med 1, 100\u2013110 (2011).","journal-title":"Nat. Med"},{"key":"1362_CR29","doi-asserted-by":"publisher","first-page":"3334","DOI":"10.1038\/sj.onc.1205398","volume":"21","author":"SG Rane","year":"2002","unstructured":"Rane, S. G. & Reddy, E. P. JAKs, STATs and Src kinases in hematopoiesis. Oncogene 21, 3334\u20133358 (2002).","journal-title":"Oncogene"},{"key":"1362_CR30","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1182\/blood.V88.5.1576.1576","volume":"5","author":"M Silva","year":"1996","unstructured":"Silva, M. et al. Erythropoietin can promote erythroid progenitor survival by repressing apoptosis through Bcl-XL and Bcl-2. Blood 5, 1576\u20131582 (1996).","journal-title":"Blood"},{"key":"1362_CR31","first-page":"E566","volume":"6","author":"AJ Casbon","year":"2015","unstructured":"Casbon, A. J. et al. Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils. Proc. Natl. Acad. Sci. USA 6, E566\u2013E575 (2015).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1362_CR32","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.1182\/blood.V90.8.3037","volume":"8","author":"JF Seymour","year":"1997","unstructured":"Seymour, J. F. et al. Mice lacking both granulocyte colony-stimulating factor (CSF) and granulocyte-macrophage CSF have impaired reproductive capacity, perturbed neonatal granulopoiesis, lung disease, amyloidosis, and reduced long-term survival. Blood 8, 3037\u20133049 (1997).","journal-title":"Blood"},{"key":"1362_CR33","doi-asserted-by":"publisher","first-page":"6503","DOI":"10.4049\/jimmunol.161.12.6503","volume":"12","author":"F Dong","year":"1998","unstructured":"Dong, F. et al. Stimulation of Stat5 by granulocyte colony-stimulating factor (G-CSF) is modulated by two distinct cytoplasmic regions of the G-CSF receptor. J. Immunol. 12, 6503\u20136509 (1998).","journal-title":"J. Immunol."},{"key":"1362_CR34","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/s12276-024-01192-4","volume":"3","author":"DAG Barisas","year":"2024","unstructured":"Barisas, D. A. G. & Choi, K. Extramedullary hematopoiesis in cancer. Exp. Mol. Med 3, 549\u2013558 (2024).","journal-title":"Exp. Mol. Med"},{"key":"1362_CR35","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/S1074-7613(03)00201-2","volume":"2","author":"T Ara","year":"2003","unstructured":"Ara, T. et al. Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity 2, 257\u2013267 (2003).","journal-title":"Immunity"},{"key":"1362_CR36","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1016\/j.immuni.2006.10.016","volume":"6","author":"T Sugiyama","year":"2006","unstructured":"Sugiyama, T., Kohara, H., Noda, M. & Nagasawa, T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 6, 977\u2013988 (2006).","journal-title":"Immunity"},{"key":"1362_CR37","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1038\/sj.leu.2402684","volume":"10","author":"T Lapidot","year":"2002","unstructured":"Lapidot, T. & Kollet, O. The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD\/SCID and NOD\/SCID\/B2m(null) mice. Leukemia 10, 1992\u20132003 (2002).","journal-title":"Leukemia"},{"key":"1362_CR38","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1189\/jlb.4CE0216-088R","volume":"2","author":"DC Dale","year":"2016","unstructured":"Dale, D. C. Editorial: The mysteries of the spleen. J. Leukoc. Biol. 2, 249\u2013251 (2016).","journal-title":"J. Leukoc. Biol."},{"key":"1362_CR39","doi-asserted-by":"crossref","unstructured":"Steenbrugge, J., De Jaeghere, E. A., Meyer, E., Denys, H. & De Wever, O. Splenic hematopoietic and stromal cells in cancer progression. Cancer Res 1, 27\u201334 (2021).","DOI":"10.1158\/0008-5472.CAN-20-2339"},{"key":"1362_CR40","doi-asserted-by":"publisher","first-page":"2723","DOI":"10.1007\/s00018-020-03450-w","volume":"14","author":"X Yang","year":"2020","unstructured":"Yang, X., Chen, D., Long, H. & Zhu, B. The mechanisms of pathological extramedullary hematopoiesis in diseases. Cell Mol. Life Sci. 14, 2723\u20132738 (2020).","journal-title":"Cell Mol. Life Sci."},{"key":"1362_CR41","doi-asserted-by":"publisher","first-page":"4221","DOI":"10.1073\/pnas.1320753111","volume":"11","author":"WC Wu","year":"2014","unstructured":"Wu, W. C. et al. Circulating hematopoietic stem and progenitor cells are myeloid-biased in cancer patients. Proc. Natl. Acad. Sci. USA 11, 4221\u20134226 (2014).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1362_CR42","doi-asserted-by":"publisher","first-page":"3425","DOI":"10.1172\/JCI97973","volume":"8","author":"C Wu","year":"2018","unstructured":"Wu, C. et al. Spleen mediates a distinct hematopoietic progenitor response supporting tumor-promoting myelopoiesis. J. Clin. Invest 8, 3425\u20133438 (2018).","journal-title":"J. Clin. Invest"},{"key":"1362_CR43","doi-asserted-by":"crossref","unstructured":"Hori, T. et al. Usefulness of palliative prognostic index, objective prognostic score, and neutrophil-lymphocyte ratio\/albumin ratio as prognostic indicators for patients without cancer receiving home-visit palliative care: A pilot study at a community general hospital. Palliat. Med. Rep. 1, 142\u2013149 (2024).","DOI":"10.1089\/pmr.2023.0096"},{"key":"1362_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75745-8","volume":"10","author":"N Iwai","year":"2020","unstructured":"Iwai, N. et al. Neutrophil to lymphocyte ratio predicts prognosis in unresectable pancreatic cancer. Sci. Rep. 10, 18758 (2020).","journal-title":"Sci. Rep."},{"key":"1362_CR45","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.ccell.2022.04.017","volume":"6","author":"JK Mandula","year":"2022","unstructured":"Mandula, J. K. & Rodriguez, P. C. Tumor-directed dysregulation of erythroid progenitors drives immunosuppressive myeloid cells. Cancer Cell 6, 597\u2013599 (2022).","journal-title":"Cancer Cell"},{"key":"1362_CR46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2417473122","volume":"9","author":"ZZ Wu","year":"2025","unstructured":"Wu, Z. Z. et al. Erythroid progenitor cell-mediated spleen-tumor interaction deteriorates cancer immunity. Proc. Natl. Acad. Sci. USA 9, e2417473122 (2025).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1362_CR47","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1097\/PAT.0b013e3283613dbf","volume":"4","author":"Y Miwa","year":"2013","unstructured":"Miwa, Y. et al. Up-regulated expression of CXCL12 in human spleens with extramedullary haematopoiesis. Pathology 4, 408\u2013416 (2013).","journal-title":"Pathology"},{"key":"1362_CR48","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1172\/JCI7615","volume":"9","author":"A Peled","year":"1999","unstructured":"Peled, A. et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34(+) cells on vascular endothelium under shear flow. J. Clin. Invest 9, 1199\u20131211 (1999).","journal-title":"J. Clin. Invest"},{"key":"1362_CR49","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/intimm\/dxy058","volume":"1","author":"T Sugiyama","year":"2019","unstructured":"Sugiyama, T., Omatsu, Y. & Nagasawa, T. Niches for hematopoietic stem cells and immune cell progenitors. Int Immunol. 1, 5\u201311 (2019).","journal-title":"Int Immunol."},{"key":"1362_CR50","doi-asserted-by":"publisher","first-page":"e3001746","DOI":"10.1371\/journal.pbio.3001746","volume":"21","author":"DAG Barisas","year":"2023","unstructured":"Barisas, D. A. G. et al. Tumor-derived interleukin-1alpha and leukemia inhibitory factor promote extramedullary hematopoiesis. PLoS Biol. 21, e3001746 (2023).","journal-title":"PLoS Biol."},{"key":"1362_CR51","doi-asserted-by":"crossref","unstructured":"Al Sayed, M. F. et al. T-cell-secreted TNFalpha induces wmergency myelopoiesis and myeloid-derived suppressor cell differentiation in cancer. Cancer Res. 2, 346\u2013359 (2019).","DOI":"10.1158\/0008-5472.CAN-17-3026"},{"key":"1362_CR52","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/nature15530","volume":"7579","author":"CN Inra","year":"2015","unstructured":"Inra, C. N. et al. A perisinusoidal niche for extramedullary haematopoiesis in the spleen. Nature 7579, 466\u2013471 (2015).","journal-title":"Nature"},{"key":"1362_CR53","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.critrevonc.2004.11.005","volume":"1","author":"V Munugalavadla","year":"2005","unstructured":"Munugalavadla, V. & Kapur, R. Role of c-Kit and erythropoietin receptor in erythropoiesis. Crit. Rev. Oncol. Hematol. 1, 63\u201375 (2005).","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"1362_CR54","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/46809","volume":"6752","author":"R De Maria","year":"1999","unstructured":"De Maria, R. et al. Negative regulation of erythropoiesis by caspase-mediated cleavage of GATA-1. Nature 6752, 489\u2013493 (1999).","journal-title":"Nature"},{"key":"1362_CR55","doi-asserted-by":"publisher","first-page":"4440","DOI":"10.1182\/blood-2002-03-0864","volume":"13","author":"A Harashima","year":"2002","unstructured":"Harashima, A. et al. CD45 tyrosine phosphatase inhibits erythroid differentiation of umbilical cord blood CD34+ cells associated with selective inactivation of Lyn. Blood 13, 4440\u20134445 (2002).","journal-title":"Blood"},{"key":"1362_CR56","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/S0167-5699(99)01506-6","volume":"9","author":"ML Thomas","year":"1999","unstructured":"Thomas, M. L. & Brown, E. J. Positive and negative regulation of Src-family membrane kinases by CD45. Immunol. Today 9, 406\u2013411 (1999).","journal-title":"Immunol. Today"},{"key":"1362_CR57","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1182\/blood-2005-09-008243","volume":"5","author":"VG Karur","year":"2006","unstructured":"Karur, V. G., Lowell, C. A., Besmer, P., Agosti, V. & Wojchowski, D. M. Lyn kinase promotes erythroblast expansion and late-stage development. Blood 5, 1524\u20131532 (2006).","journal-title":"Blood"},{"key":"1362_CR58","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.1182\/blood-2016-05-718320","volume":"23","author":"X Gao","year":"2016","unstructured":"Gao, X. et al. TGF-beta inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors. Blood 23, 2637\u20132641 (2016).","journal-title":"Blood"},{"key":"1362_CR59","first-page":"1394","volume":"5","author":"K Matsuzaki","year":"2000","unstructured":"Matsuzaki, K. et al. Autocrine stimulatory mechanism by transforming growth factor beta in human hepatocellular carcinoma. Cancer Res 5, 1394\u20131402 (2000).","journal-title":"Cancer Res"},{"key":"1362_CR60","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1016\/S0140-6736(03)14567-9","volume":"9392","author":"M Henke","year":"2003","unstructured":"Henke, M. et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 9392, 1255\u20131260 (2003).","journal-title":"Lancet"},{"key":"1362_CR61","doi-asserted-by":"publisher","first-page":"eabb0130","DOI":"10.1126\/scitranslmed.abb0130","volume":"13","author":"Y Hou","year":"2021","unstructured":"Hou, Y. et al. Radiotherapy and immunotherapy converge on elimination of tumor-promoting erythroid progenitor cells through adaptive immunity. Sci. Transl. Med 13, eabb0130 (2021).","journal-title":"Sci. Transl. Med"},{"key":"1362_CR62","doi-asserted-by":"publisher","first-page":"2699","DOI":"10.1007\/s00204-025-04036-w","volume":"7","author":"WT Hu","year":"2025","unstructured":"Hu, W. T. et al. A silence catalyst: CCL5-mediated intercellular communication in cancer. Arch. Toxicol. 7, 2699\u20132712 (2025).","journal-title":"Arch. Toxicol."},{"key":"1362_CR63","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/s41580-022-00456-z","volume":"7","author":"H Sies","year":"2022","unstructured":"Sies, H. et al. Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nat. Rev. Mol. Cell Biol. 7, 499\u2013515 (2022).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1362_CR64","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1093\/jimmun\/vkaf020","volume":"6","author":"S Elahi","year":"2025","unstructured":"Elahi, S. et al. Galectin-3 regulates erythropoiesis and enhances the immunoregulatory properties of CD71+ erythroid cells across developmental stages. J. Immunol. 6, 1202\u20131218 (2025).","journal-title":"J. Immunol."},{"key":"1362_CR65","doi-asserted-by":"publisher","first-page":"112840","DOI":"10.1016\/j.biopha.2022.112840","volume":"149","author":"F Niu","year":"2022","unstructured":"Niu, F. et al. Arginase: An emerging and promising therapeutic target for cancer treatment. Biomed. Pharmacother. 149, 112840 (2022).","journal-title":"Biomed. Pharmacother."},{"key":"1362_CR66","doi-asserted-by":"crossref","unstructured":"Delyea, C. et al. CD71(+) erythroid suppressor cells promote fetomaternal tolerance through arginase-2 and PDL-1. J. Immunol. 12, 4044\u20134058 (2018).","DOI":"10.4049\/jimmunol.1800113"},{"key":"1362_CR67","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1111\/bjh.19914","volume":"2","author":"K Czubak","year":"2025","unstructured":"Czubak, K. et al. CD71(+) erythroid cells promote multiple myeloma progression and impair anti-bacterial immune response. Br. J. Haematol. 2, 478\u2013483 (2025).","journal-title":"Br. J. Haematol."},{"key":"1362_CR68","doi-asserted-by":"crossref","unstructured":"Ohl, K. & Tenbrock, K. Reactive oxygen species as regulators of MDSC-mediated immune suppression. Front Immunol. 9, 2499 (2018).","DOI":"10.3389\/fimmu.2018.02499"},{"key":"1362_CR69","doi-asserted-by":"crossref","unstructured":"Dubaniewicz, A. Mycobacterial heat shock proteins in sarcoidosis and tuberculosis. Int J. Mol. Sci. 24, 5084 (2023).","DOI":"10.3390\/ijms24065084"},{"key":"1362_CR70","doi-asserted-by":"crossref","unstructured":"Rotem, S. et al. A novel approach to vaccine development: Concomitant pathogen inactivation and host immune stimulation by peroxynitrite. Vaccines (Basel) 10, 1593 (2022).","DOI":"10.3390\/vaccines10101593"},{"key":"1362_CR71","doi-asserted-by":"publisher","first-page":"3106","DOI":"10.4049\/jimmunol.0902661","volume":"6","author":"S Nagaraj","year":"2010","unstructured":"Nagaraj, S., Schrum, A. G., Cho, H. I., Celis, E. & Gabrilovich, D. I. Mechanism of T cell tolerance induced by myeloid-derived suppressor cells. J. Immunol. 6, 3106\u20133116 (2010).","journal-title":"J. Immunol."},{"key":"1362_CR72","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1381919","volume":"15","author":"X Fan","year":"2024","unstructured":"Fan, X. et al. Tumor-associated CD8(+)T cell tolerance induced by erythroid progenitor cells. Front Immunol. 15, 1381919 (2024).","journal-title":"Front Immunol."},{"key":"1362_CR73","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1056\/NEJMoa1200694","volume":"26","author":"JR Brahmer","year":"2012","unstructured":"Brahmer, J. R. et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med 26, 2455\u20132465 (2012).","journal-title":"N. Engl. J. Med"},{"key":"1362_CR74","doi-asserted-by":"crossref","unstructured":"Boucher, J. C. et al. CD28 costimulatory domain-targeted mutations enhance chimeric antigen receptor T-cell function. Cancer Immunol. Res. 1, 62\u201374 (2021).","DOI":"10.1158\/2326-6066.CIR-20-0253"},{"key":"1362_CR75","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12571","volume":"52","author":"R Zhao","year":"2019","unstructured":"Zhao, R. et al. PD-1\/PD-L1 blockade rescue exhausted CD8+ T cells in gastrointestinal stromal tumours via the PI3K\/Akt\/mTOR signalling pathway. Cell Prolif. 52, e12571 (2019).","journal-title":"Cell Prolif."},{"key":"1362_CR76","doi-asserted-by":"publisher","first-page":"3015","DOI":"10.1084\/jem.20090847","volume":"13","author":"LM Francisco","year":"2009","unstructured":"Francisco, L. M. et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J. Exp. Med 13, 3015\u20133029 (2009).","journal-title":"J. Exp. Med"},{"key":"1362_CR77","doi-asserted-by":"crossref","unstructured":"Nazarov, K. et al. Murine placental erythroid cells are mainly represented by CD45(+) immunosuppressive erythroid cells and secrete CXCL1, CCL2, CCL3 and CCL4 chemokines. Int J. Mol. Sci. 24, 8130 (2023).","DOI":"10.3390\/ijms24098130"},{"key":"1362_CR78","doi-asserted-by":"crossref","unstructured":"Geiger, R. et al. L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell 167, 829\u2013842.e13 (2016).","DOI":"10.1016\/j.cell.2016.09.031"},{"key":"1362_CR79","doi-asserted-by":"publisher","first-page":"21123","DOI":"10.1074\/jbc.M110675200","volume":"24","author":"PC Rodriguez","year":"2002","unstructured":"Rodriguez, P. C. et al. Regulation of T cell receptor CD3zeta chain expression by L-arginine. J. Biol. Chem. 24, 21123\u201321129 (2002).","journal-title":"J. Biol. Chem."},{"key":"1362_CR80","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1182\/blood-2006-06-031856","volume":"4","author":"PC Rodriguez","year":"2007","unstructured":"Rodriguez, P. C., Quiceno, D. G. & Ochoa, A. C. L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood 4, 1568\u20131573 (2007).","journal-title":"Blood"},{"key":"1362_CR81","doi-asserted-by":"publisher","first-page":"13139","DOI":"10.18632\/oncotarget.11487","volume":"17","author":"JE Unterlass","year":"2018","unstructured":"Unterlass, J. E. et al. Validating and enabling phosphoglycerate dehydrogenase (PHGDH) as a target for fragment-based drug discovery in PHGDH-amplified breast cancer. Oncotarget 17, 13139\u201313153 (2018).","journal-title":"Oncotarget"},{"key":"1362_CR82","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1182\/blood-2006-11-010389","volume":"5","author":"M Munder","year":"2006","unstructured":"Munder, M. et al. Suppression of T-cell functions by human granulocyte arginase. Blood 5, 1627\u20131634 (2006).","journal-title":"Blood"},{"key":"1362_CR83","doi-asserted-by":"publisher","first-page":"4583","DOI":"10.4049\/jimmunol.175.7.4583","volume":"7","author":"S Kusmartsev","year":"2005","unstructured":"Kusmartsev, S., Nagaraj, S. & Gabrilovich, D. I. Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J. Immunol. 7, 4583\u20134592 (2005).","journal-title":"J. Immunol."},{"key":"1362_CR84","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s13045-022-01349-6","volume":"15","author":"X Shi","year":"2022","unstructured":"Shi, X. et al. TGF-beta signaling in the tumor metabolic microenvironment and targeted therapies. J. Hematol. Oncol. 15, 135 (2022).","journal-title":"J. Hematol. Oncol."},{"key":"1362_CR85","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1038\/nri2808","volume":"8","author":"RA Flavell","year":"2010","unstructured":"Flavell, R. A., Sanjabi, S., Wrzesinski, S. H. & Licona-Limon, P. The polarization of immune cells in the tumour environment by TGFbeta. Nat. Rev. Immunol. 8, 554\u2013567 (2010).","journal-title":"Nat. Rev. Immunol."},{"key":"1362_CR86","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1007\/s00262-004-0652-3","volume":"9","author":"F Weber","year":"2005","unstructured":"Weber, F. et al. Transforming growth factor-beta1 immobilises dendritic cells within skin tumours and facilitates tumour escape from the immune system. Cancer Immunol. Immunother. 9, 898\u2013906 (2005).","journal-title":"Cancer Immunol. Immunother."},{"key":"1362_CR87","doi-asserted-by":"publisher","first-page":"e2006649","DOI":"10.1371\/journal.pbio.2006649","volume":"16","author":"S Shahbaz","year":"2018","unstructured":"Shahbaz, S. et al. CD71+VISTA+ erythroid cells promote the development and function of regulatory T cells through TGF-beta. PLoS Biol. 16, e2006649 (2018).","journal-title":"PLoS Biol."},{"key":"1362_CR88","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41571-018-0142-8","volume":"3","author":"JS O\u2019Donnell","year":"2019","unstructured":"O\u2019Donnell, J. S., Teng, M. W. L. & Smyth, M. J. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat. Rev. Clin. Oncol. 3, 151\u2013167 (2019).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"1362_CR89","doi-asserted-by":"crossref","unstructured":"Wang, C. et al. Tumor-associated myeloid cells selective delivery of a therapeutic tumor nano-vaccine for overcoming immune barriers for effective and long-term cancer immunotherapy. Adv. Health. Mater. 13, e2401416 (2024).","DOI":"10.1002\/adhm.202401416"},{"key":"1362_CR90","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2016.80","volume":"5","author":"T Gargett","year":"2016","unstructured":"Gargett, T. et al. GM-CSF signalling blockade and chemotherapeutic agents act in concert to inhibit the function of myeloid-derived suppressor cells in vitro. Clin. Transl. Immunol. 5, e119 (2016).","journal-title":"Clin. Transl. Immunol."},{"key":"1362_CR91","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1002\/iub.2192","volume":"1","author":"L Gutierrez","year":"2020","unstructured":"Gutierrez, L., Caballero, N., Fernandez-Calleja, L., Karkoulia, E. & Strouboulis, J. Regulation of GATA1 levels in erythropoiesis. IUBMB Life 1, 89\u2013105 (2020).","journal-title":"IUBMB Life"},{"key":"1362_CR92","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1038\/s41375-019-0420-1","volume":"5","author":"A Bataller","year":"2019","unstructured":"Bataller, A., Montalban-Bravo, G., Soltysiak, K. A. & Garcia-Manero, G. The role of TGFbeta in hematopoiesis and myeloid disorders. Leukemia 5, 1076\u20131089 (2019).","journal-title":"Leukemia"},{"key":"1362_CR93","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1002\/ajh.23786","volume":"10","author":"X Zhang","year":"2014","unstructured":"Zhang, X. et al. FOXO3-mTOR metabolic cooperation in the regulation of erythroid cell maturation and homeostasis. Am. J. Hematol. 10, 954\u2013963 (2014).","journal-title":"Am. J. Hematol."},{"key":"1362_CR94","doi-asserted-by":"publisher","first-page":"6964","DOI":"10.1182\/bloodadvances.2023010561","volume":"22","author":"K Gustafsson","year":"2023","unstructured":"Gustafsson, K. et al. Clearing and replacing tissue-resident myeloid cells with an anti-CD45 antibody-drug conjugate. Blood Adv. 22, 6964\u20136973 (2023).","journal-title":"Blood Adv."},{"key":"1362_CR95","first-page":"e135751","volume":"5","author":"L Yang","year":"2020","unstructured":"Yang, L. et al. Regulation of bile duct epithelial injury by hepatic CD71+ erythroid cells. JCI Insight 5, e135751 (2020).","journal-title":"JCI Insight"},{"key":"1362_CR96","doi-asserted-by":"crossref","unstructured":"Bai, D., Zhou, Y., Jing, L., Guo, C. & Yang, Q. Arginine metabolism in cancer biology and immunotherapy. Immune Netw. 25, e30 (2025).","DOI":"10.4110\/in.2025.25.e30"},{"key":"1362_CR97","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/s41568-021-00435-0","volume":"5","author":"EC Cheung","year":"2022","unstructured":"Cheung, E. C. & Vousden, K. H. The role of ROS in tumour development and progression. Nat. Rev. Cancer 5, 280\u2013297 (2022).","journal-title":"Nat. Rev. Cancer"},{"key":"1362_CR98","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01831-w","volume":"22","author":"Y Ren","year":"2023","unstructured":"Ren, Y. et al. Multifaceted role of redox pattern in the tumor immune microenvironment regarding autophagy and apoptosis. Mol. Cancer 22, 130 (2023).","journal-title":"Mol. Cancer"},{"key":"1362_CR99","doi-asserted-by":"crossref","unstructured":"Grzywa, T. M. et al. Myeloid cell-derived arginase in cancer immune response. Front Immunol. 11, 938 (2020).","DOI":"10.3389\/fimmu.2020.00938"},{"key":"1362_CR100","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2025.189465","volume":"1880","author":"Y Zhang","year":"2025","unstructured":"Zhang, Y., Lyu, J. & Fang, H. Rewiring amino acids in cancer. Biochim Biophys. Acta Rev. Cancer 1880, 189465 (2025).","journal-title":"Biochim Biophys. Acta Rev. Cancer"},{"key":"1362_CR101","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq6221","volume":"15","author":"S Cane","year":"2023","unstructured":"Cane, S. et al. Neutralization of NET-associated human ARG1 enhances cancer immunotherapy. Sci. Transl. Med 15, eabq6221 (2023).","journal-title":"Sci. Transl. Med"},{"key":"1362_CR102","doi-asserted-by":"crossref","unstructured":"Elahi, S. Neglected cells: Immunomodulatory roles of CD71(+) erythroid cells. Trends Immunol. 40, 181\u2013185 (2019).","DOI":"10.1016\/j.it.2019.01.003"},{"key":"1362_CR103","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104536","volume":"204","author":"ZZ Li","year":"2024","unstructured":"Li, Z. Z., Zhou, K., Wu, Q., Liu, B. & Bu, L. L. Lymph node metastasis in cancer: Clearing the clouds to see the dawn. Crit. Rev. Oncol. Hematol. 204, 104536 (2024).","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"1362_CR104","doi-asserted-by":"crossref","unstructured":"Sano, Y. et al. Multiorgan signaling mobilizes tumor-associated erythroid cells expressing immune checkpoint molecules. Mol. Cancer Res. 3, 507\u2013515 (2021).","DOI":"10.1158\/1541-7786.MCR-20-0746"}],"container-title":["npj Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01362-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01362-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01362-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T01:02:18Z","timestamp":1776733338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01362-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,8]]},"references-count":104,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1362"],"URL":"https:\/\/doi.org\/10.1038\/s41698-026-01362-9","relation":{},"ISSN":["2397-768X"],"issn-type":[{"value":"2397-768X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,8]]},"assertion":[{"value":"23 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 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","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"163"}}