{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T04:51:31Z","timestamp":1794027091751,"version":"4.8.0"},"reference-count":48,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T00:00:00Z","timestamp":1694390400000},"content-version":"unspecified","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Shanghai Sailing Program","award":["21YF1403900"],"award-info":[{"award-number":["21YF1403900"]}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["23ZR1408300"],"award-info":[{"award-number":["23ZR1408300"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072881"],"award-info":[{"award-number":["82072881"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203665"],"award-info":[{"award-number":["82203665"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273205"],"award-info":[{"award-number":["82273205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["22Y31900502"],"award-info":[{"award-number":["22Y31900502"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,8,10]]},"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The potent immunosuppressive properties of sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on myeloid cells and lymphocytes provide a strong rationale for serving as a therapeutic target. However, the expression profile and critical role of Siglec-9 in high-grade serous ovarian cancer (HGSC) remain obscure. This study aimed to elucidate the prognostic significance of Siglec-9 expression and its predictive value for immunotherapy in HGSC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Study enrolled two cohorts, consisting of 120 tumor microarray specimens of HGSC for immunohistochemistry (IHC) and 40 fresh tumor specimens for flow cytometry (FCM). Expression profile of Siglec-9 in immune cells was analyzed by both bioinformatics analysis and FCM. Role of Siglec-9 was studied to identify that Siglec-9<jats:sup>+<\/jats:sup>TAMs linked with an immunosuppressive phenotype by IHC and FCM, and block Siglec-9 was sensitive to immunotherapy by ex vivo and in vitro assays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Siglec-9 is predominantly expressed on tumor-associated macrophages (TAMs). High Siglec-9<jats:sup>+<\/jats:sup>TAMs were associated with inferior overall survival (OS). Both tumor-conditioned medium (TCM) and tumor ascites induced enrichment of Siglec-9<jats:sup>+<\/jats:sup>TAMs with protumorigenic phenotypes. Siglec-9<jats:sup>+<\/jats:sup>TAMs were associated with immunosuppressive tumor microenvironment (TME) characterized by exhausted CD8<jats:sup>+<\/jats:sup>T cells and increased immune checkpoint expression. Blockade of Siglec-9 suppressed phosphorylation of the inhibitory phosphatase SHP-1 and repolarized TAMs to antitumorigenic phenotype and retrieved cytotoxic activity of CD8<jats:sup>+<\/jats:sup>T cells in vitro and ex vivo. Responders toward antiprogrammed death receptor-1 (anti-PD-1) therapy present more Siglec-9<jats:sup>+<\/jats:sup>TAMs than non-responders. Furthermore, blockade Siglec-9 synergized with anti-PD-1 antibody to enhance the cytotoxic activity of CD8<jats:sup>+<\/jats:sup>T cells in tissues with higher Siglec-9<jats:sup>+<\/jats:sup>TAMs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Siglec-9<jats:sup>+<\/jats:sup>TAMs may serve as an independent prognostic of poor survival but a predictive biomarker for anti-PD-1\/antiprogrammed death ligand-1 immunotherapy in HGSC. In addition, the potential of immunosuppressive Siglec-9<jats:sup>+<\/jats:sup>TAMs as a therapeutic target is worth further exploration.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2023-007099","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T01:00:35Z","timestamp":1694653235000},"page":"e007099","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Siglec-9<sup>+<\/sup> tumor-associated macrophages delineate an immunosuppressive subset with therapeutic vulnerability in patients with high-grade serous ovarian cancer"],"prefix":"10.1136","volume":"11","author":[{"given":"Yiying","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 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