{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T18:39:46Z","timestamp":1793817586165,"version":"4.6.1"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008730","name":"Kreftforeningen","doi-asserted-by":"publisher","award":["215850"],"award-info":[{"award-number":["215850"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008730","name":"Kreftforeningen","doi-asserted-by":"publisher","award":["298910"],"award-info":[{"award-number":["298910"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007793","name":"Stiftelsen Kristian Gerhard Jebsen","doi-asserted-by":"publisher","award":["19"],"award-info":[{"award-number":["19"]}],"id":[{"id":"10.13039\/100007793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    PI3K inhibitors (PI3Ki) have shown promise in some hematological cancers, but further development has been hampered by reports of serious immune\u2010related adverse effects. Thus, identification of effective PI3Ki lacking these adverse effects is desirable. Here, we evaluated the\n                    <jats:italic>in vitro<\/jats:italic>\n                    effects of the investigational PI3Ki roginolisib (IOA\u2010244) and the approved PI3Ki idelalisib on immune cells and leukemic cells. Roginolisib inhibited chronic lymphocytic leukemia cell signaling and viability in a manner comparable to idelalisib. Both drugs specifically inhibited PI3K\u2010signaling in T\u00a0cells, validating their on\u2010target effects. Both idelalisib and roginolisib reduced regulatory T\u2010cell frequency in a concentration\u2010dependent manner, with idelalisib demonstrating greater potency. Both inhibitors also reduced T\u2010cell activation and proliferation, but to differing extents. However, only idelalisib induced a pronounced impairment of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell cytotoxic function. Furthermore, idelalisib treatment promoted differentiation of conventional CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells into Th1, Th2, and Th17 subsets\u2014a response not observed with roginolisib. In summary, roginolisib functions as an effective PI3K inhibitor on leukemic cells while preserving T\u2010cell functions, posing it as an alternative to current PI3K inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70203","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T11:43:02Z","timestamp":1769082182000},"page":"1612-1625","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The\n                    <scp>PI3K\u03b4<\/scp>\n                    inhibitor roginolisib (\n                    <scp>IOA<\/scp>\n                    \u2010244) preserves T\u2010cell function and activity"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3073-8878","authenticated-orcid":false,"given":"Elise","family":"Solli","sequence":"first","affiliation":[{"name":"Department of Cancer Immunology Institute for Cancer Research, Oslo University Hospital  Norway"},{"name":"KG Jebsen Centre for B\u2010cell Malignancies, Institute of Clinical Medicine, University of Oslo  Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Bevilacqua","sequence":"additional","affiliation":[{"name":"iOnctura SA  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Wenes","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Geneva  Switzerland"},{"name":"Center for Translational Research in Onco\u2010Hematology, University of Geneva  Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Migliorini","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Geneva  Switzerland"},{"name":"Center for Translational Research in Onco\u2010Hematology, University of Geneva  Switzerland"},{"name":"Department of Oncology Geneva University Hospitals (HUG)  Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"van der Veen","sequence":"additional","affiliation":[{"name":"iOnctura BV  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1630-356X","authenticated-orcid":false,"given":"Sigrid S","family":"Sk\u00e5nland","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology Institute for Cancer Research, Oslo University Hospital  Norway"},{"name":"KG Jebsen Centre for B\u2010cell Malignancies, Institute of Clinical Medicine, University of Oslo  Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1353-5867","authenticated-orcid":false,"given":"Giusy","family":"Di Conza","sequence":"additional","affiliation":[{"name":"iOnctura SA  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2841-4697","authenticated-orcid":false,"given":"Kjetil","family":"Task\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology Institute for Cancer Research, Oslo University Hospital  Norway"},{"name":"KG Jebsen Centre for B\u2010cell Malignancies, Institute of Clinical Medicine, University of Oslo  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flow cytometry with fluorescent cell barcoding for single cell signaling analysis and biomarker discovery","volume":"140","author":"Sk\u00e5nland SS","year":"2018","journal-title":"J Vis 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