| Literature DB >> 35879361 |
Johanna F Dekkers1,2,3, Maria Alieva2,3, Astrid Cleven4, Farid Keramati2, Amber K L Wezenaar2,3, Esmée J van Vliet2,3, Jens Puschhof1,3,5, Peter Brazda2, Inez Johanna4, Angelo D Meringa4, Heggert G Rebel2,3, Maj-Britt Buchholz2,3, Mario Barrera Román2,3, Amber L Zeeman2,3, Sam de Blank2,3, Domenico Fasci4, Maarten H Geurts1,3, Annelisa M Cornel2,4, Else Driehuis1,3, Rosemary Millen1,3, Trudy Straetemans4,6, Mara J T Nicolasen4, Tineke Aarts-Riemens4, Hendrikus C R Ariese2,3, Hannah R Johnson2,3, Ravian L van Ineveld2,3, Froso Karaiskaki4, Oded Kopper1,3, Yotam E Bar-Ephraim1,3, Kai Kretzschmar1,3,7, Alexander M M Eggermont2,8,9, Stefan Nierkens2,4, Ellen J Wehrens2,3, Henk G Stunnenberg2, Hans Clevers1,2,3,10, Jürgen Kuball4,6, Zsolt Sebestyen4, Anne C Rios11,12.
Abstract
Extending the success of cellular immunotherapies against blood cancers to the realm of solid tumors will require improved in vitro models that reveal therapeutic modes of action at the molecular level. Here we describe a system, called BEHAV3D, developed to study the dynamic interactions of immune cells and patient cancer organoids by means of imaging and transcriptomics. We apply BEHAV3D to live-track >150,000 engineered T cells cultured with patient-derived, solid-tumor organoids, identifying a 'super engager' behavioral cluster comprising T cells with potent serial killing capacity. Among other T cell concepts we also study cancer metabolome-sensing engineered T cells (TEGs) and detect behavior-specific gene signatures that include a group of 27 genes with no previously described T cell function that are expressed by super engager killer TEGs. We further show that type I interferon can prime resistant organoids for TEG-mediated killing. BEHAV3D is a promising tool for the characterization of behavioral-phenotypic heterogeneity of cellular immunotherapies and may support the optimization of personalized solid-tumor-targeting cell therapies.Entities:
Year: 2022 PMID： 35879361 DOI： 10.1038/s41587-022-01397-w
Source DB: PubMed Journal: Nat Biotechnol ISSN： 1087-0156 Impact factor: 68.164