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

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