Immunogenomic analysis of human brain metastases reveals diverse immune landscapes across genetically distinct tumors

Ángel F Álvarez-Prado; Roeltje R Maas; Klara Soukup; Florian Klemm; Mara Kornete; Fanny S Krebs; Vincent Zoete; Sabina Berezowska; Jean-Philippe Brouland; Andreas F Hottinger; Roy T Daniel; Monika E Hegi; Johanna A Joyce

doi:10.1016/j.xcrm.2022.100900

Immunogenomic analysis of human brain metastases reveals diverse immune landscapes across genetically distinct tumors

Cell Rep Med. 2023 Jan 17;4(1):100900. doi: 10.1016/j.xcrm.2022.100900.

Authors

Affiliations

¹ Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
² Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; Neuroscience Research Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
³ Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center, 1011 Lausanne, Switzerland.
⁴ Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁵ Department of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
⁶ Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; Brain and Spine Tumor Center, Departments of Clinical Neurosciences and Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
⁷ L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
⁸ L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; Neuroscience Research Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
⁹ Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland. Electronic address: johanna.joyce@unil.ch.

Abstract

Brain metastases (BrMs) are the most common form of brain tumors in adults and frequently originate from lung and breast primary cancers. BrMs are associated with high mortality, emphasizing the need for more effective therapies. Genetic profiling of primary tumors is increasingly used as part of the effort to guide targeted therapies against BrMs, and immune-based strategies for the treatment of metastatic cancer are gaining momentum. However, the tumor immune microenvironment (TIME) of BrM is extremely heterogeneous, and whether specific genetic profiles are associated with distinct immune states remains unknown. Here, we perform an extensive characterization of the immunogenomic landscape of human BrMs by combining whole-exome/whole-genome sequencing, RNA sequencing of immune cell populations, flow cytometry, immunofluorescence staining, and tissue imaging analyses. This revealed unique TIME phenotypes in genetically distinct lung- and breast-BrMs, thereby enabling the development of personalized immunotherapies tailored by the genetic makeup of the tumors.

Keywords: T cells; brain metastasis; cancer immunology; genomics; immunogenomics; microglia; monocyte-derived macrophages; neutrophils; transcriptomics; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Brain Neoplasms* / genetics
Breast Neoplasms* / genetics
Breast Neoplasms* / pathology
Female
Humans
Immunotherapy
Melanoma*
Skin Neoplasms*
Tumor Microenvironment / genetics

Grants and funding

J 4343/FWF_/Austrian Science Fund FWF/Austria