期刊
SCIENCE ADVANCES
卷 8, 期 26, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abn9440
关键词
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资金
- Swiss National Science Foundation Professorial Fellowship [PP00P3_176974]
- ProPatient Forschungsstiftung
- University Hospital Basel (Annemarie Karrasch Award 2019)
- Department of Surgery, University Hospital Basel
- Brain Tumour Charity Foundation, London, UK [GN-000562]
- U.S. NIH [5U54CA20997103, IDIQ17X149]
- U.S. DOD [W81XWH-14-1-0180]
- U.S. FDA [DSTL/AGR/00980/01]
- Cancer Research UK [C27165/A29073]
- Bill and Melinda Gates Foundation [OPP1113682]
- Parker Institute for Cancer Immunotherapy
- Beckman Center for Molecular and Genetic Medicine
- Swiss National Science Foundation [P300PB_171189, P400PM_183915]
- Lady Tata Memorial Trust, London, UK
- UICC Technical Fellowship [TF/18/625070]
- NIH [AR007422, 5T32AI007290-34, CA233203]
- Stanford Dean's Postdoctoral Fellowship
- Stanford's Dermatology Department
- Stanford Bio-X Interdisciplinary Graduate Fellowship
- Stanford's Bioengineering Department
- Rachford & Carlotta A. Harris Endowed Chair
- Swiss National Science Foundation (SNF) [P400PM_183915, P300PB_171189, PP00P3_176974] Funding Source: Swiss National Science Foundation (SNF)
This study demonstrated that ex vivo immunotherapy of GBM explants can induce an active antitumoral immune response within the tumor center, providing a framework for multidimensional personalized assessment of tumor response to immunotherapy.
A patient-tailored, ex vivo drug response platform for glioblastoma ( GBM) would facilitate therapy planning, provide insights into treatment-induced mechanisms in the immune tumor microenvironment (iTME), and enable the discovery of biomarkers of response. We cultured regionally annotated GBM explants in perfusion bioreactors to assess iTME responses to immunotherapy. Explants were treated with anti-CD47, anti-PD-1, or their combination, and analyzed by multiplexed microscopy [CO-Detection by indEXing (CODEX)], enabling the spatially resolved identification of >850,000 single cells, accompanied by explant secretome interrogation. Center and periphery explants differed in their cell type and soluble factor composition, and responses to immunotherapy. A subset of explants displayed increased interferon-gamma levels, which correlated with shifts in immune cell composition within specified tissue compartments. Our study demonstrates that ex vivo immunotherapy of GBM explants enables an active antitumoral immune response within the tumor center and provides a framework for multidimensional personalized assessment of tumor response to immunotherapy.
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