EconPapers    
Economics at your fingertips  
 

Barcoded viral tracing identifies immunosuppressive astrocyte–glioma interactions

Brian M. Andersen, Camilo Faust Akl, Michael A. Wheeler, Zhaorong Li, Martin Diebold, Michael Kilian, Joseph M. Rone, Aditya Misra, Jessica E. Kenison, Joon-Hyuk Lee, Hong-Gyun Lee, Carolina M. Polonio, David Merrell, Jakob H. Weiss, Lillie Godinez, Gavin Piester, Tomer Illouz, Jessica J. Ye, Arianna Ghia, Jazmin Martinez, Elizabeth N. Chung, Lena Srun, Daniel Farrenkopf, Lucas E. Flausino, Anton M. Schüle, Liliana M. Sanmarco, Federico Giovannoni, Luca Fehrenbacher, Marc Charabati, Cristina Gutiérrez-Vázquez, Margaret M. Cusick, Prem S. Prabhakar, Connor C. Bossi, Emily Lapinskas, Roni Nowarski, Gad Getz, Keith L. Ligon, Marco Prinz, E. Antonio Chiocca, David A. Reardon and Francisco J. Quintana ()
Additional contact information
Brian M. Andersen: Harvard Medical School
Camilo Faust Akl: Harvard Medical School
Michael A. Wheeler: Harvard Medical School
Zhaorong Li: Harvard Medical School
Martin Diebold: University of Freiburg
Michael Kilian: Harvard Medical School
Joseph M. Rone: Harvard Medical School
Aditya Misra: Harvard Medical School
Jessica E. Kenison: Harvard Medical School
Joon-Hyuk Lee: Harvard Medical School
Hong-Gyun Lee: Harvard Medical School
Carolina M. Polonio: Harvard Medical School
David Merrell: Broad Institute of MIT and Harvard
Jakob H. Weiss: Broad Institute of MIT and Harvard
Lillie Godinez: Harvard Medical School
Gavin Piester: Harvard Medical School
Tomer Illouz: Harvard Medical School
Jessica J. Ye: Harvard Medical School
Arianna Ghia: Harvard Medical School
Jazmin Martinez: Harvard Medical School
Elizabeth N. Chung: Harvard Medical School
Lena Srun: Harvard Medical School
Daniel Farrenkopf: Harvard Medical School
Lucas E. Flausino: Harvard Medical School
Anton M. Schüle: Harvard Medical School
Liliana M. Sanmarco: Harvard Medical School
Federico Giovannoni: Harvard Medical School
Luca Fehrenbacher: University of Freiburg
Marc Charabati: Harvard Medical School
Cristina Gutiérrez-Vázquez: Harvard Medical School
Margaret M. Cusick: Harvard Medical School
Prem S. Prabhakar: Harvard Medical School
Connor C. Bossi: Harvard Medical School
Emily Lapinskas: Harvard Medical School
Roni Nowarski: Harvard Medical School
Gad Getz: Broad Institute of MIT and Harvard
Keith L. Ligon: Harvard Medical School
Marco Prinz: University of Freiburg
E. Antonio Chiocca: Brigham and Women’s Hospital, Harvard Medical School
David A. Reardon: Harvard Medical School
Francisco J. Quintana: Harvard Medical School

Nature, 2025, vol. 644, issue 8078, 1097-1106

Abstract: Abstract Glioblastoma (GBM) is the most lethal primary brain malignancy1. Immunosuppression in the GBM tumour microenvironment (TME) is an important barrier to immune-targeted therapies, but our understanding of the mechanisms of immune regulation in the GBM TME is limited2. Here we describe a viral barcode interaction-tracing approach3 to analyse TME cell–cell communication in GBM clinical samples and preclinical models at single-cell resolution. We combine it with single-cell and bulk RNA-sequencing analyses, human organotypic GBM cultures, in vivo cell-specific CRISPR–Cas9-driven genetic perturbations as well as human and mouse experimental systems to identify an annexin A1–formyl peptide receptor 1 (ANXA1–FPR1) bidirectional astrocyte–GBM communication pathway that limits tumour-specific immunity. FPR1 inhibits immunogenic necroptosis in tumour cells, and ANXA1 suppresses NF-κB and inflammasome activation in astrocytes. ANXA1 expression in astrocytes and FPR1 expression in cancer cells are associated with poor outcomes in individuals with GBM. The inactivation of astrocyte–glioma ANXA1–FPR1 signalling enhanced dendritic cell, T cell and macrophage responses, increasing infiltration by tumour-specific CD8+ T cells and limiting T cell exhaustion. In summary, we have developed a method to analyse TME cell–cell interactions at single-cell resolution in clinical samples and preclinical models, and used it to identify bidirectional astrocyte–GBM communication through ANXA1–FPR1 as a driver of immune evasion and tumour progression.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-025-09191-9 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:644:y:2025:i:8078:d:10.1038_s41586-025-09191-9

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-025-09191-9

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().

 
Page updated 2025-08-29
Handle: RePEc:nat:nature:v:644:y:2025:i:8078:d:10.1038_s41586-025-09191-9