Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function

Augusto Faria Andrade, Alva Annett, Elham Karimi, Danai Georgia Topouza, Morteza Rezanejad, Yitong Liu, Michael McNicholas, Eduardo G. Gonzalez Santiago, Dhana Llivichuzhca-Loja, Arne Gehlhaar, Selin Jessa, Antonella Cola, Bhavyaa Chandarana, Caterina Russo, Damien Faury, Geoffroy Danieau, Evan Puligandla, Yuhong Wei, Michele Zeinieh, Qing Wu, Steven Hebert, Nikoleta Juretic, Emily M. Nakada, Brian Krug, Valerie Larouche, Alexander G. Weil, Roy W. R. Dudley, Jason Karamchandani, Sameer Agnihotri, Daniela F. Quail, Benjamin Ellezam, Liza Konnikova (), Logan A. Walsh, Manav Pathania (), Claudia L. Kleinman () and Nada Jabado ()
Additional contact information
Augusto Faria Andrade: McGill University
Alva Annett: McGill University
Elham Karimi: McGill University
Danai Georgia Topouza: McGill University
Morteza Rezanejad: University of Toronto
Yitong Liu: McGill University
Michael McNicholas: University of Cambridge
Eduardo G. Gonzalez Santiago: Yale School of Medicine
Dhana Llivichuzhca-Loja: Yale School of Medicine
Arne Gehlhaar: University of Bonn
Selin Jessa: McGill University
Antonella Cola: University of Cambridge
Bhavyaa Chandarana: McGill University
Caterina Russo: The Research Institute of the McGill University Health Centre
Damien Faury: The Research Institute of the McGill University Health Centre
Geoffroy Danieau: The Research Institute of the McGill University Health Centre
Evan Puligandla: McGill University
Yuhong Wei: McGill University
Michele Zeinieh: McGill University
Qing Wu: The Research Institute of the McGill University Health Centre
Steven Hebert: McGill University
Nikoleta Juretic: The Research Institute of the McGill University Health Centre
Emily M. Nakada: The Research Institute of the McGill University Health Centre
Brian Krug: McGill University
Valerie Larouche: Centre mère-enfant Soleil du CHU de Québec-Université Laval
Alexander G. Weil: Sainte-Justine Research Centre
Roy W. R. Dudley: McGill University
Jason Karamchandani: McGill University
Sameer Agnihotri: University of Pittsburgh School of Medicine
Daniela F. Quail: McGill University
Benjamin Ellezam: Université de Montréal
Liza Konnikova: Yale School of Medicine
Logan A. Walsh: McGill University
Manav Pathania: University of Cambridge
Claudia L. Kleinman: McGill University
Nada Jabado: McGill University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), particularly the immune infiltrate. Here, we characterize the immune TME of H3.3K27M and G34R/V-mutant gliomas, and multiple H3.3K27M mouse models, using transcriptomic, proteomic and spatial single-cell approaches. Resolution of immune lineages indicates high infiltration of H3-mutant gliomas with diverse myeloid populations, high-level expression of immune checkpoint markers, and scarce lymphoid cells, findings uniformly reproduced in all H3.3K27M mouse models tested. We show these myeloid populations communicate with H3-mutant cells, mediating immunosuppression and sustaining tumor formation and maintenance. Dual inhibition of myeloid cells and immune checkpoint pathways show significant therapeutic benefits in pre-clinical syngeneic mouse models. Our findings provide a valuable characterization of the TME of oncohistone-mutant gliomas, and insight into the means for modulating the myeloid infiltrate for the benefit of patients.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-52096-w Abstract (text/html)

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:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52096-w

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

DOI: 10.1038/s41467-024-52096-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

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