{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T17:01:27Z","timestamp":1761238887124,"version":"3.37.3"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70113307"],"award-info":[{"award-number":["70113307"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG EXC2151 \u2013 390873048"],"award-info":[{"award-number":["DFG EXC2151 \u2013 390873048"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008131","name":"Rheinische Friedrich-Wilhelms-Universit\u00e4t Bonn","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008131","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The PI3K\u03b4-inhibitor Idelalisib is approved for the treatment of Non-Hodgkin lymphoma. However, its use has been decreased within the last years due to deleterious infections such as cytomegalovirus and pneumocystis jirovecii. Here, we have investigated the effect of Idelalisib on human monocyte-derived dendritic cells (DCs) as important players in the induction of immune responses. We found that Idelalisib-treated DCs displayed impaired T cell stimulatory function. PI3K\u03b4 inhibition during differentiation resulted in decreased Interleukin-12, Interleukin-13 and TNF\u03b1 production by DCs after lipopolysaccharide stimulation. Moreover, DCs showed decreased expression of the activation marker CD83 after Idelalisib treatment. Further, in line with this was the failure of Idelalisib-treated DCs to properly induce allogeneic T cells in a dose-dependent manner. Finally, activation of the NF\u03baB pathway was also ablated in Idelalisib-treated DCs. Our results implicate that severe infectious complications may not only result from direct PI3K\u03b4-inhibition in T cells, but also from impaired DC function in Idelalisib-treated patients. Here, we provide new insight into the pathogenesis of Idelalisib-associated infectious complications. Our study may further provide a rationale for the use of Idelalisib as a novel therapeutic option in inflammatory diseases.<\/jats:p>","DOI":"10.1007\/s00262-021-02988-3","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T19:03:31Z","timestamp":1624647811000},"page":"3693-3700","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The PI3K\u03b4 inhibitor idelalisib impairs the function of human dendritic cells"],"prefix":"10.1007","volume":"70","author":[{"given":"Christiane","family":"Braun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3239-5444","authenticated-orcid":false,"given":"Sebastian","family":"Schlaweck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solveig Nora","family":"Daecke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Brossart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annkristin","family":"Heine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"2988_CR1","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/S0140-6736(16)32407-2","volume":"390","author":"JO Armitage","year":"2017","unstructured":"Armitage JO, Gascoyne RD, Lunning MA, Cavalli F (2017) Non-hodgkin lymphoma. The Lancet 390:298\u2013310. https:\/\/doi.org\/10.1016\/S0140-6736(16)32407-2","journal-title":"The Lancet"},{"key":"2988_CR2","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1182\/blood-2010-02-271171","volume":"116","author":"SEM Herman","year":"2010","unstructured":"Herman SEM, Gordon AL, Wagner AJ et al (2010) Phosphatidylinositol 3-kinase-\u03b4 inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood 116:2078\u20132088. https:\/\/doi.org\/10.1182\/blood-2010-02-271171","journal-title":"Blood"},{"key":"2988_CR3","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1056\/NEJMoa1315226","volume":"370","author":"RR Furman","year":"2014","unstructured":"Furman RR, Sharman JP, Coutre SE et al (2014) Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. 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(#173\/09).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}