{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:28:11Z","timestamp":1792618091270,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006356","name":"Syddansk Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006356","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Glioblastoma is the most malignant primary brain tumour. Even with standard treatment comprising surgery followed by radiation and concomitant temozolomide (TMZ) chemotherapy, glioblastoma remains incurable. Almost all patients with glioblastoma relapse owing to various intrinsic and extrinsic resistance mechanisms of the tumour cells. Glioblastomas are densely infiltrated with tumour\u2010associated microglia and macrophages (TAMs). These immune cells affect the tumour cells in experimental studies and are associated with poor patient survival in clinical studies. The aim of the study was to investigate the impact of microglia on glioblastoma chemo\u2010resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We co\u2010cultured patient\u2010derived glioblastoma spheroids with microglia at different TMZ concentrations and analysed cell death. In addition, we used RNA sequencing to explore differentially expressed genes after co\u2010culture. Immunostaining was used for validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Co\u2010culture experiments showed that microglia significantly increased TMZ resistance in glioblastoma cells. RNA sequencing revealed upregulation of a clear interferon\u2010stimulated gene (ISG) expression signature in the glioblastoma cells after co\u2010culture with microglia, including genes such as\n                      <jats:italic>IFI6<\/jats:italic>\n                      ,\n                      <jats:italic>IFI27<\/jats:italic>\n                      ,\n                      <jats:italic>BST2<\/jats:italic>\n                      ,\n                      <jats:italic>MX1<\/jats:italic>\n                      and\n                      <jats:italic>STAT1<\/jats:italic>\n                      . This ISG expression signature is linked to STAT1 signalling, which was confirmed by immunostaining. The ISG expression profile observed in glioblastoma cells with enhanced TMZ resistance corresponded to the interferon\u2010related DNA damage resistance signature (IRDS) described in different solid cancers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Here, we show that the IRDS signature, linked to chemo\u2010resistance in other cancers, can be induced in glioblastoma by microglia. ISG genes and the microglia inducing the ISG expression could be promising novel therapeutic targets in glioblastoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.13016","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T01:14:55Z","timestamp":1731978895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Microglia induce an interferon\u2010stimulated gene expression profile in glioblastoma and increase glioblastoma resistance to temozolomide"],"prefix":"10.1111","volume":"50","author":[{"given":"Mia Dahl","family":"S\u00f8rensen","sequence":"first","affiliation":[{"name":"Department of Pathology Odense University Hospital  Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke Frydendahl Sick","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Pathology Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Burton","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital  Odense Denmark"},{"name":"Clinical Genome Center, Department of Clinical Research University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Kavan","sequence":"additional","affiliation":[{"name":"Department of Clinical Research University of Southern Denmark  Odense Denmark"},{"name":"Department of Clinical Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine Asferg","family":"Petterson","sequence":"additional","affiliation":[{"name":"Department of Pathology Odense University Hospital  Odense 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