{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:24:28Z","timestamp":1790976268740,"version":"4.1.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:00:00Z","timestamp":1676851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81872143"],"award-info":[{"award-number":["81872143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["20JCQNJC01400"],"award-info":[{"award-number":["20JCQNJC01400"]}]},{"DOI":"10.13039\/501100013077","name":"National Science and Technology Support Project of China","doi-asserted-by":"crossref","award":["2018ZX09201015"],"award-info":[{"award-number":["2018ZX09201015"]}],"id":[{"id":"10.13039\/501100013077","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Project of Science and Technology of Tianjin","award":["18JCQNJC82700"],"award-info":[{"award-number":["18JCQNJC82700"]}]},{"DOI":"10.13039\/501100019062","name":"Tianjin Research Innovation Project for Postgraduate Students","doi-asserted-by":"crossref","award":["2021YJSB261"],"award-info":[{"award-number":["2021YJSB261"]}],"id":[{"id":"10.13039\/501100019062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Early-stage myeloid-derived suppressor cells are a newly defined subset of myeloid-derived suppressor cells in breast cancer tissues and related to poor prognosis in patients with breast cancer. Compared with classical myeloid-derived suppressor cells, early-stage myeloid-derived suppressor cells display exceptional immunosuppressive ability and accumulate in the tumor microenvironment to suppress innate and adaptive immunity. Previously, we demonstrated that early-stage myeloid-derived suppressor cells were SOCS3 deficiency dependent and correlated with differentiation arrest in the myeloid lineage. Autophagy is a major regulator of myeloid differentiation, but the mechanism by which autophagy regulates the development of early-stage myeloid-derived suppressor cells has not been elucidated. Here, we constructed EO771 mammary tumor-bearing conditional myeloid SOCS3 knockout mice (SOCS3MyeKO) characterized by abundant tumor-infiltrating early-stage myeloid-derived suppressor cells and exacerbated immunosuppression in vitro and in vivo. We found that early-stage myeloid-derived suppressor cells isolated from SOCS3MyeKO mice showed differentiation arrest in the myeloid lineage, which was caused by limited autophagy activation in an Wnt\/mTOR-dependent manner. RNA sequencing and microRNA microarray assays revealed that miR-155\u2013induced C\/EBP\u03b2 downregulation activated the Wnt\/mTOR pathway and promoted autophagy repression and differentiation arrest in early-stage myeloid-derived suppressor cells. Furthermore, inhibition of Wnt\/mTOR signaling suppressed both tumor growth and the immunosuppressive functions of early-stage myeloid-derived suppressor cells. Thus, SOCS3 deficiency-dependent autophagy repression and their regulatory mechanisms could contribute to the immunosuppressive tumor microenvironment. Our study proposes a novel mechanism for promoting early-stage myeloid-derived suppressor cell survival, which might shed new light on a potential target of oncologic therapy.<\/jats:p>","DOI":"10.1093\/jleuko\/qiad020","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T12:27:36Z","timestamp":1676896056000},"page":"445-460","source":"Crossref","is-referenced-by-count":19,"title":["SOCS3 deficiency-dependent autophagy repression promotes the survival of early-stage myeloid-derived suppressor cells in breast cancer by activating the Wnt\/mTOR pathway"],"prefix":"10.1093","volume":"113","author":[{"given":"Wenwen","family":"Zhang","sequence":"first","affiliation":[{"name":"Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Department of Organ Transplantation Center, Tianjin First Central Hospital, School of Medicine, Nankai University , Fukang Road, Nankai District, Tianjin 300192 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchen","family":"Li","sequence":"additional","affiliation":[{"name":"Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Tianjin Third Central Hospital , Jintang Road, Hedong District, Tianjin 300170 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyan","family":"Ji","sequence":"additional","affiliation":[{"name":"Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guidong","family":"Chen","sequence":"additional","affiliation":[{"name":"Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengpeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiubao","family":"Ren","sequence":"additional","affiliation":[{"name":"Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research, Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research, Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinpu","family":"Yu","sequence":"additional","affiliation":[{"name":"Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"},{"name":"Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer , Huanhuxi Road, Hexi District, Tianjin 300060 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"issue":"1","key":"2023050220195639400_qiad020-B1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.tips.2018.10.008","article-title":"MDSC; the most important cell you have never heard of","volume":"40","author":"Tesi","year":"2019","journal-title":"Trends Pharmacol Sci"},{"issue":"4","key":"2023050220195639400_qiad020-B2","first-page":"992","article-title":"Targeting myeloid-derived suppressor cells for cancer therapy","volume":"18","author":"Tang","year":"2021","journal-title":"Cancer Biol 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