{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:56:50Z","timestamp":1791309410214,"version":"4.3.1"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFA0915700"],"award-info":[{"award-number":["2023YFA0915700"]}]},{"name":"National Natural Science Foundation of China","award":["32230034"],"award-info":[{"award-number":["32230034"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["32322031"],"award-info":[{"award-number":["32322031"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82488101"],"award-info":[{"award-number":["82488101"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["32571071"],"award-info":[{"award-number":["32571071"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["2023B1111020005"],"award-info":[{"award-number":["2023B1111020005"]}]},{"name":"Open Fund Project of Guangdong Academy of Medical Sciences","award":["YKY-KF202207"],"award-info":[{"award-number":["YKY-KF202207"]}],"id":[{"id":"https:\/\/ror.org\/0432p8t34","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Science and Technology Planning Project of Guangdong Province","award":["2023B1212060028"],"award-info":[{"award-number":["2023B1212060028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Splenic myelopoiesis supplies immunosuppressive myeloid cells in cancer, yet its local regulation remains unclear. Here we identify a self-amplifying circuit between neutrophils and hematopoietic stem and progenitor cells (HSPCs) that sustains splenic myelopoiesis. Tumor-associated neutrophils produced reactive oxygen species (ROS) and created an oxidatively stressed milieu in the spleen, which activated FOXO1 in neighboring HSPCs and drove DRP1-mediated mitochondrial fission, reprogramming HSPCs toward myeloid-biased expansion and immunosuppressive output. Progeny neutrophils reinforced splenic oxidative stress and perpetuated this loop. Genetic ablation of\n                    <jats:italic>Cybb<\/jats:italic>\n                    or spleen-targeted ROS scavenging inhibited FOXO1 activation and preserved fused mitochondria morphology in HSPCs. Consistently, blockade of FOXO1 or DRP1 prevented mitochondrial fission and reduced ROS-producing myeloid cell generation. Such interventions reduced splenic myelopoiesis, curtailed the production of suppressive myeloid cells in the spleen and their infiltration into tumors, and enhanced cytotoxic T cell activity, thereby restoring antitumor immunity and restraining tumor progression. Analyses of spleen samples from cancer patients, together with cord-blood HSPC and neutrophil co-culture experiments, support the human relevance of this neutrophil\u2013ROS\u2013HSPC axis. These findings reveal a self-propagating neutrophil\u2013HSPC feedback circuit that locally sustains tumor-promoting splenic myelopoiesis and provide a rationale for targeting neutrophil-to-progenitor signaling to normalize antitumor immunity.\n                  <\/jats:p>","DOI":"10.1172\/jci204067","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:46:58Z","timestamp":1791308818000},"source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil-progenitor feedback sustains splenic myelopoiesis and promotes immune evasion in cancer"],"prefix":"10.1172","author":[{"given":"Lan","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Life Sciences, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufeng","family":"Luo","sequence":"additional","affiliation":[{"name":"Xiangya Cancer Center, Central South University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaomin","family":"Hua","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-An","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Lin","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Guangdong Provincial People\u2019s Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huolun","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Guangdong Provincial People\u2019s Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Guangdong Provincial People\u2019s Hospital, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9593-293X","authenticated-orcid":true,"given":"Chong","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8281-1450","authenticated-orcid":true,"given":"Limin","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,9,29]]},"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.jci.org\/articles\/view\/204067\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:47:00Z","timestamp":1791308820000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jci.org\/articles\/view\/204067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":0,"alternative-id":["10.1172\/JCI204067"],"URL":"https:\/\/doi.org\/10.1172\/jci204067","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]}}}