Microenvironmental Landscape of Human Melanoma Brain Metastases in Response to Immune Checkpoint Inhibition.
Journal
Cancer immunology research
ISSN: 2326-6074
Titre abrégé: Cancer Immunol Res
Pays: United States
ID NLM: 101614637
Informations de publication
Date de publication:
03 08 2022
03 08 2022
Historique:
received:
12
10
2021
revised:
12
01
2022
accepted:
08
06
2022
pubmed:
17
6
2022
medline:
5
8
2022
entrez:
16
6
2022
Statut:
ppublish
Résumé
Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently an end stage of the disease. Immune checkpoint inhibitors (ICI) provide a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique elements of the MBM TME and correlates of MBM response to ICI, we collected 32 fresh MBM and performed single-cell RNA sequencing of the MBM TME and T-cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions. We observed myeloid phenotypic heterogeneity in the MBM TME, most notably multiple distinct neutrophil states, including an IL8-expressing population that correlated with malignant cell epithelial-to-mesenchymal transition. In addition, we observed significant relationships between intracranial T-cell phenotypes and the distribution of T-cell clonotypes intracranially and peripherally. We found that the phenotype, clonotype, and overall number of MBM-infiltrating T cells were associated with response to ICI, suggesting that ICI-responsive MBMs interact with peripheral blood in a manner similar to extracranial lesions. These data identify unique features of the MBM TME that may represent potential targets to improve clinical outcomes for patients with MBM.
Identifiants
pubmed: 35706413
pii: 704915
doi: 10.1158/2326-6066.CIR-21-0870
pmc: PMC10201927
mid: NIHMS1818207
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
996-1012Subventions
Organisme : NCI NIH HHS
ID : R37 CA258829
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA263381
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227156
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA244975
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221703
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224070
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA220253
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA248960
Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
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