Immunogenomic analysis of human brain metastases reveals diverse immune landscapes across genetically distinct tumors.
T cells
brain metastasis
cancer immunology
genomics
immunogenomics
microglia
monocyte-derived macrophages
neutrophils
transcriptomics
tumor microenvironment
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
17 01 2023
17 01 2023
Historique:
received:
04
05
2022
revised:
20
09
2022
accepted:
19
12
2022
entrez:
18
1
2023
pubmed:
19
1
2023
medline:
21
1
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36652909
pii: S2666-3791(22)00479-7
doi: 10.1016/j.xcrm.2022.100900
pmc: PMC9873981
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100900Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests F.K. is currently an employee at Sophia Genetics; V.Z. is a consultant for Cellestia Biotech; S.B. has received honoraria from Eli Lilly (Advisory Board) and research funding to the institution from Roche and Basilea (last 3 years); M.E.H. has an advisory role at TME Pharma; J.A.J. has received honoraria for speaking at research symposia organized by Bristol Meyers Squibb and Glenmark Pharmaceuticals (last 3 years) and currently serves on the scientific advisory board of Pionyr Immunotherapeutics.
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