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000307548 1001_ $$aBessler, Nils$$b0
000307548 245__ $$aDe novo H3.3K27M-altered diffuse midline glioma in human brainstem organoids to dissect GD2 CAR T cell function.
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000307548 520__ $$aDiffuse midline glioma (DMG) is a highly aggressive and untreatable pediatric cancer primarily arising in the pontine brainstem region, necessitating the development of representative models for treatment advance. Here we developed an FGF4-driven human brainstem organoid model, which we used to genetically engineer H3.3K27M-altered DMG. We demonstrated that brainstem pontine glial specification is critical for DMG tumorigenesis, yielding infiltrative tumors that recapitulate patient-representative intratumoral heterogeneity. Prolonged GD2 chimeric antigen receptor (CAR) T cell treatment mirrored clinical outcomes and revealed extensive transcriptional heterogeneity, from which both potent effector and dysfunctional CAR T cell populations could be identified. Furthermore, incorporation of myeloid cells generated DMG-specific microglia that reduced treatment efficacy and revealed CAR T cell functional states most vulnerable to microglia-mediated immunosuppression. Thus, we present a representative DMG model offering a months-long experimental window in vitro, which we leveraged to delineate CAR T cell functionality and microglial impact, aiding therapy development for this devastating disease.
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000307548 7001_ $$00000-0002-1638-1851$$aWezenaar, Amber K L$$b1
000307548 7001_ $$00000-0002-1796-1292$$aAriese, Hendrikus C R$$b2
000307548 7001_ $$00000-0003-0167-3541$$aHonhoff, Celina$$b3
000307548 7001_ $$aDommann, Noëlle$$b4
000307548 7001_ $$aWehrens, Ellen J$$b5
000307548 7001_ $$00000-0001-9689-7964$$aRuiz Moreno, Cristian$$b6
000307548 7001_ $$00000-0003-3034-6160$$avan den Broek, Thijs J M$$b7
000307548 7001_ $$aCollot, Raphaël V U$$b8
000307548 7001_ $$aKloosterman, Daan J$$b9
000307548 7001_ $$aKeramati, Farid$$b10
000307548 7001_ $$0P:(DE-HGF)0$$aRoosen, Mieke$$b11
000307548 7001_ $$00000-0003-2191-5675$$ade Blank, Sam$$b12
000307548 7001_ $$00000-0002-9301-1598$$avan Vliet, Esmée$$b13
000307548 7001_ $$00000-0002-5919-2962$$aBarrera Román, Mario$$b14
000307548 7001_ $$aGatti, Lucrezia C D E$$b15
000307548 7001_ $$aErtürk, Ali$$b16
000307548 7001_ $$aKuball, Jürgen$$b17
000307548 7001_ $$aSebestyén, Zsolt$$b18
000307548 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b19$$udkfz
000307548 7001_ $$00000-0003-1898-1516$$aPatrizi, Sara$$b20
000307548 7001_ $$00000-0002-4747-1032$$aMiele, Evelina$$b21
000307548 7001_ $$00000-0002-8406-5412$$aKünkele, Annette$$b22
000307548 7001_ $$00000-0001-9683-7494$$aKranendonk, Mariëtte E G$$b23
000307548 7001_ $$00000-0001-8349-121X$$aCornel, Annelisa M$$b24
000307548 7001_ $$aNierkens, Stefan$$b25
000307548 7001_ $$00000-0003-3152-5574$$aMayer, Christian$$b26
000307548 7001_ $$00000-0002-0066-1576$$aStunnenberg, Hendrik G$$b27
000307548 7001_ $$00000-0002-0795-0290$$aAlemany, Anna$$b28
000307548 7001_ $$00000-0002-1425-9908$$aAlieva, Maria$$b29
000307548 7001_ $$00000-0002-9082-8068$$aRios, Anne C$$b30
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