Nature Communications (Sep 2024)
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 De 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,
- Nada Jabado
Affiliations
- Augusto Faria Andrade
- Department of Human Genetics, McGill University
- Alva Annett
- Department of Human Genetics, McGill University
- Elham Karimi
- Rosalind and Morris Goodman Cancer Institute, McGill University
- Danai Georgia Topouza
- Department of Human Genetics, McGill University
- Morteza Rezanejad
- Departments of Psychology and Computer Science, University of Toronto
- Yitong Liu
- Rosalind and Morris Goodman Cancer Institute, McGill University
- Michael McNicholas
- Department of Oncology and The Milner Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge
- Eduardo G. Gonzalez Santiago
- Department of Pediatrics, Yale School of Medicine
- Dhana Llivichuzhca-Loja
- Department of Pediatrics, Yale School of Medicine
- Arne Gehlhaar
- Life and Medical Sciences Institute, University of Bonn
- Selin Jessa
- Quantitative Life Sciences, McGill University
- Antonella De Cola
- Department of Oncology and The Milner Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge
- Bhavyaa Chandarana
- Department of Human Genetics, 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
- Cancer Research Program, The Research Institute of the McGill University Health Centre
- Evan Puligandla
- Department of Human Genetics, McGill University
- Yuhong Wei
- Rosalind and Morris Goodman Cancer Institute, McGill University
- Michele Zeinieh
- Department of Human Genetics, McGill University
- Qing Wu
- The Research Institute of the McGill University Health Centre
- Steven Hebert
- Department of Human Genetics, 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
- Department of Human Genetics, McGill University
- Valerie Larouche
- Department of Pediatrics, Centre mère-enfant Soleil du CHU de Québec-Université Laval
- Alexander G. Weil
- Brain and Development Research Axis, Sainte-Justine Research Centre
- Roy W. R. Dudley
- Department of Pediatric Surgery, Division of Neurosurgery, Montreal Children’s Hospital, McGill University
- Jason Karamchandani
- Department of Pathology, Montreal Neurological Institute, McGill University
- Sameer Agnihotri
- Department of Neurological Surgery, University of Pittsburgh School of Medicine
- Daniela F. Quail
- Rosalind and Morris Goodman Cancer Institute, McGill University
- Benjamin Ellezam
- Division of Pathology, Department of Pathology and Cell Biology, CHU Sainte-Justine, Université de Montréal
- Liza Konnikova
- Department of Pediatrics, Yale School of Medicine
- Logan A. Walsh
- Department of Human Genetics, McGill University
- Manav Pathania
- Department of Oncology and The Milner Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge
- Claudia L. Kleinman
- Department of Human Genetics, McGill University
- Nada Jabado
- Department of Human Genetics, McGill University
- DOI
- https://doi.org/10.1038/s41467-024-52096-w
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
