{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360021393552493440.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1136/jitc-2019-000308"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1136/jitc-2019-000308"}}],"dc:title":[{"@value":"Interferon gamma inhibits CXCL8–CXCR2 axis mediated tumor-associated macrophages tumor trafficking and enhances anti-PD1 efficacy in pancreatic cancer"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>Pancreatic cancer (PC) is a common malignancy of the digestive system and is characterized by poor prognosis and early metastasis. Tumor immune escape plays an important role in PC progression. Programmed death 1 (PD1) blockade therapy is a promising treatment for patients with PC, but is yet to achieve significant clinical effects so far. Interferon gamma (IFN-γ) is a soluble dimeric cytokine that is closely associated with tumor immune surveillance and cytotoxicity. IFN-γ suppresses a variety of tumor-derived cytokines in PC, such as CXCL8. In the present study, we investigated the therapeutic efficacy of combined anti-PD1 and IFN-γ treatment in PC.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>BxPC-3 and Panc-1 human PC cell lines were used to construct a murine PC model. Blood samples (n=44) and surgical resection specimens (n=36) from human patients with PC were also collected. χ<jats:sup>2</jats:sup> test, two-tailed unpaired t-test or Kaplan-Meier survival analysis was used to calculate p values.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>PD1/PD-L1 signaling was overexpressed in PC tumor-bearing mice. Anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 treatment showed limited benefit. Murine PC model had a preferential expansion of CXCR2<jats:sup>+</jats:sup>CD68<jats:sup>+</jats:sup> macrophages, and these cells showed an immunosuppressive nature (M2 polarization). PC tumors overexpressed CXCL8 and tumor-derived CXCL8 deficiency prohibited the trafficking of CXCR2<jats:sup>+</jats:sup>CD68<jats:sup>+</jats:sup> macrophages. IFN-γ suppressed the expression of tumor-derived CXCL8, and combined with IFN-γ treatment, delayed anti-PD1 treatment showed significant antitumor effects. Thus, we conclude that murine CXCR2<jats:sup>+</jats:sup>CD68<jats:sup>+</jats:sup> macrophages traffic to PC tumors by tumor-derived CXCL8 and mediate local immunosuppression, which limits the efficacy of PD1 blockade therapy. IFN-γ suppresses tumor-derived CXCL8 and inhibits the tumor trafficking of CXCR2<jats:sup>+</jats:sup>CD68<jats:sup>+</jats:sup> macrophages by blocking the CXCL8–CXCR2 axis to enhance anti-PD1 efficacy. Human PC also produces high levels of CXCL8. Patients with PC present elevated CXCR2 expression on peripheral and tumor-infiltrating CD68<jats:sup>+</jats:sup> macrophages, which are associated with advanced tumor stage and poor prognosis.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>Our findings suggest that IFN-γ is a translatable, therapeutic option to improve the efficacy of PD1 blockade therapy by preventing trafficking of CXCR2<jats:sup>+</jats:sup>CD68<jats:sup>+</jats:sup> macrophages via blocking the CXCL8–CXCR2 axis.</jats:p>\n               </jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380021393552493446","@type":"Researcher","foaf:name":[{"@value":"Guoliang Cao"}],"jpcoar:affiliationName":[{"@value":"Department of Hepatobiliary and Pancreatic Surgery, Huzhou Central Hospital, Huzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493450","@type":"Researcher","foaf:name":[{"@value":"Xu Sun"}],"jpcoar:affiliationName":[{"@value":"Department of Hepatobiliary and Pancreatic Surgery, Huzhou Central Hospital, Huzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493448","@type":"Researcher","foaf:name":[{"@value":"Mingjie Zhang"}],"jpcoar:affiliationName":[{"@value":"Department of Hepatobiliary and Pancreatic Surgery, Huzhou Central Hospital, Huzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493443","@type":"Researcher","foaf:name":[{"@value":"Neng Lou"}],"jpcoar:affiliationName":[{"@value":"Department of Hepatobiliary and Pancreatic Surgery, Huzhou Central Hospital, Huzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493441","@type":"Researcher","foaf:name":[{"@value":"Qiang Wei"}],"jpcoar:affiliationName":[{"@value":"Department of Hepatobiliary and Pancreatic Surgery, Huzhou Central Hospital, Huzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493444","@type":"Researcher","foaf:name":[{"@value":"Tao Shen"}],"jpcoar:affiliationName":[{"@value":"Department of Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493445","@type":"Researcher","foaf:name":[{"@value":"Xiaodong Xu"}],"jpcoar:affiliationName":[{"@value":"Department of Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493449","@type":"Researcher","foaf:name":[{"@value":"Liping Cao"}],"jpcoar:affiliationName":[{"@value":"Department of Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493447","@type":"Researcher","foaf:name":[{"@value":"Qiang Yan"}],"jpcoar:affiliationName":[{"@value":"Department of Hepatobiliary and Pancreatic Surgery, Huzhou Central Hospital, Huzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493440","@type":"Researcher","foaf:name":[{"@value":"Lifeng Huang"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Biomedicine and Health, Hangzhou Normal University Hangzhou School of Medicine, Hangzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493442","@type":"Researcher","foaf:name":[{"@value":"Guoping Ding"}],"jpcoar:affiliationName":[{"@value":"Department of Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393552493451","@type":"Researcher","foaf:name":[{"@value":"Huilian Huang"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou, China"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20511426"}],"prism:publicationName":[{"@value":"Journal for ImmunoTherapy of Cancer"}],"dc:publisher":[{"@value":"BMJ"}],"prism:publicationDate":"2020-02","prism:volume":"8","prism:number":"1","prism:startingPage":"e000308"},"reviewed":"false","dc:rights":["http://creativecommons.org/licenses/by-nc/4.0/"],"url":[{"@id":"https://syndication.highwire.org/content/doi/10.1136/jitc-2019-000308"}],"createdAt":"2020-02-12","modifiedAt":"2025-10-03","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360584340716969344","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Intratumoral delivery of a highly active form of <scp>XCL1</scp> enhances antitumor <scp>CTL</scp> responses through recruitment of <scp>CXCL9</scp>‐expressing conventional type‐1 dendritic cells"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1136/jitc-2019-000308"},{"@type":"CROSSREF","@value":"10.1002/ijc.34874_references_DOI_RedeQrQ4zhMV9r4RVwA4uXLZtxJ"}]}