Immunotherapy of glioblastoma explants induces interferon-γ responses and spatial immune cell rearrangements in tumor center, but not periphery-Reference-Cited by-同舟云学术

Immunotherapy of glioblastoma explants induces interferon-γ responses and spatial immune cell rearrangements in tumor center, but not periphery

Published:2022-07 Issue:26 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Shekarian Tala¹^ORCID,Zinner Carl P.¹²^ORCID,Bartoszek Ewelina M.¹^ORCID,Duchemin Wandrille³^ORCID,Wachnowicz Anna T.¹^ORCID,Hogan Sabrina¹^ORCID,Etter Manina M.¹^ORCID,Flammer Julia¹,Paganetti Chiara¹,Martins Tomas A.¹^ORCID,Schmassmann Philip¹^ORCID,Zanganeh Steven⁴^ORCID,Le Goff Francois⁵^ORCID,Muraro Manuele G.⁶^ORCID,Ritz Marie-Françoise¹⁷,Phillips Darci⁸⁹¹⁰^ORCID,Bhate Salil S.⁹¹⁰^ORCID,Barlow Graham L.⁹¹⁰^ORCID,Nolan Garry P.¹⁰,Schürch Christian M.⁹¹⁰¹¹^ORCID,Hutter Gregor¹⁷^ORCID

Affiliation:

1. Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland.

2. Institute of Medical Genetics and Pathology, University Hospital and University of Basel, Basel, Switzerland.

3. sciCORE Center for Scientific Computing, University of Basel, Basel, Switzerland.

4. Department of Bioengineering, University of Massachusetts Dartmouth, Dartmouth, MA, USA.

5. Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland.

6. Tissue Engineering Laboratory, Department of Biomedicine, University Hospital of Basel and University of Basel, Basel, Switzerland.

7. Department of Neurosurgery, University Hospital Basel, Basel, Switzerland.

8. Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.

9. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.

10. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.

11. Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany.

Abstract

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-γ 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference48 articles.

1. Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma

2. Immunology in the clinic review series; focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment

3. Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies

4. CSF-1R inhibition alters macrophage polarization and blocks glioma progression

5. Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma

Cited by 28 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Cancer organoids 2.0: modelling the complexity of the tumour immune microenvironment;Nature Reviews Cancer;2024-07-08

2. L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial;Nature Communications;2024-05-28

3. Cellular diversity through space and time: adding new dimensions to GBM therapeutic development;Frontiers in Genetics;2024-05-07

4. In situ characterization of the tumor microenvironment;Current Opinion in Biotechnology;2024-04

5. A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma;2024-03-08