{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:39:31Z","timestamp":1792373971725,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI\u2010EX107\u201010706BI"],"award-info":[{"award-number":["NHRI\u2010EX107\u201010706BI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI\u2010EX108\u201010706BI"],"award-info":[{"award-number":["NHRI\u2010EX108\u201010706BI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI\u2010EX109\u201010706BI"],"award-info":[{"award-number":["NHRI\u2010EX109\u201010706BI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI\u2010EX114\u201011219BI"],"award-info":[{"award-number":["NHRI\u2010EX114\u201011219BI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["TCVGH\u2010NHRI\u2010113008"],"award-info":[{"award-number":["TCVGH\u2010NHRI\u2010113008"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["TCVGH\u2010NHRI\u2010114002"],"award-info":[{"award-number":["TCVGH\u2010NHRI\u2010114002"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012544","name":"China Medical University, Taiwan","doi-asserted-by":"publisher","award":["CMU113\u2010MF\u201034"],"award-info":[{"award-number":["CMU113\u2010MF\u201034"]}],"id":[{"id":"10.13039\/501100012544","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012544","name":"China Medical University, Taiwan","doi-asserted-by":"publisher","award":["CMU114\u2010MF\u201003"],"award-info":[{"award-number":["CMU114\u2010MF\u201003"]}],"id":[{"id":"10.13039\/501100012544","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lung cancer\u2010mediated myeloid\u2010derived suppressor cell (MDSC) inhibits antitumour immunity for tumour progression and is a promising target. Here, we present the ADAM9\u2010targeting therapeutic strategy to unleash anticancer immunity. We identified a novel role for ADAM9 in promoting lung cancer immunosuppression through the upregulation of cytokines that drive the recruitment and expansion of MDSCs, with CXCL12 serving as one of the major mediators. This ADAM9\u2013CXCL12\u2013MDSC axis significantly impairs the function of cytotoxic CD8+ T cells. Disrupting the ADAM9\u2013CXCL12 axis suppresses oncogenic signalling pathways, including EGFR and IL\u20106 signalling. Therapeutically, the developed ADAM9 inhibitors significantly reduced primary tumour growth and metastasis in syngeneic mouse models of lung tumours, concurrent with remodelling of the immune microenvironment. This study demonstrates that ADAM9 promotes cancer\u2010mediated MDSC function by enhancing CXCL12 production. Targeting ADAM9 represents a novel and effective strategy to reverse the immunosuppressive tumour microenvironment and suppress lung cancer progression.<\/jats:p>","DOI":"10.1111\/imm.70212","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:43:01Z","timestamp":1792370581000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ADAM9<\/scp>\n                    Regulation of\n                    <scp>CXCL12<\/scp>\n                    \u2010Dependent Myeloid\u2010Derived Suppressor Cells Shifting the Immune Landscape of Lung Adenocarcinoma"],"prefix":"10.1111","author":[{"given":"Jing\u2010Pei","family":"Liu","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2359-5532","authenticated-orcid":false,"given":"Wan\u2010Ling","family":"Wu","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology National Health Research Institutes  Miaoli Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan\u2010Yin","family":"Shen","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology National Health Research Institutes  Miaoli Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Ting","family":"Kuo","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine China Medical University Hospital  Taichung 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China Medical University  Taichung Taiwan"},{"name":"Cancer Biology and Precision Therapeutics Center China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray F.","year":"2024","journal-title":"CA: A Cancer Journal for Clinicians"},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"12150","DOI":"10.1038\/ncomms12150","article-title":"Recommendations for Myeloid\u2010Derived Suppressor Cell Nomenclature and Characterization Standards","volume":"7","author":"Bronte V.","year":"2016","journal-title":"Nature Communications"},{"key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10555-020-09947-x","article-title":"Role of 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