Basal-to-inflammatory transition and tumor resistance via crosstalk with a pro-inflammatory stromal niche.
Humans
Tumor Microenvironment
/ immunology
Animals
Inflammation
/ pathology
Mice
Cell Line, Tumor
Carcinoma, Squamous Cell
/ pathology
Carcinoma, Basal Cell
/ pathology
Drug Resistance, Neoplasm
Triggering Receptor Expressed on Myeloid Cells-1
/ metabolism
Stromal Cells
/ pathology
NF-kappa B
/ metabolism
Single-Cell Analysis
Gene Expression Regulation, Neoplastic
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 Sep 2024
17 Sep 2024
Historique:
received:
24
01
2024
accepted:
05
09
2024
medline:
18
9
2024
pubmed:
18
9
2024
entrez:
17
9
2024
Statut:
epublish
Résumé
Cancer-associated inflammation is a double-edged sword possessing both pro- and anti-tumor properties through ill-defined tumor-immune dynamics. While we previously identified a carcinoma tumor-intrinsic resistance pathway, basal-to-squamous cell carcinoma transition, here, employing a multipronged single-cell and spatial-omics approach, we identify an inflammation and therapy-enriched tumor state we term basal-to-inflammatory transition. Basal-to-inflammatory transition signature correlates with poor overall patient survival in many epithelial tumors. Basal-to-squamous cell carcinoma transition and basal-to-inflammatory transition occur in adjacent but distinct regions of a single tumor: basal-to-squamous cell carcinoma transition arises within the core tumor nodule, while basal-to-inflammatory transition emerges from a specialized inflammatory environment defined by a tumor-associated TREM1 myeloid signature. TREM1 myeloid-derived cytokines IL1 and OSM induce basal-to-inflammatory transition in vitro and in vivo through NF-κB, lowering sensitivity of patient basal cell carcinoma explant tumors to Smoothened inhibitor treatment. This work deepens our knowledge of the heterogeneous local tumor microenvironment and nominates basal-to-inflammatory transition as a drug-resistant but targetable tumor state driven by a specialized inflammatory microenvironment.
Identifiants
pubmed: 39289380
doi: 10.1038/s41467-024-52394-3
pii: 10.1038/s41467-024-52394-3
doi:
Substances chimiques
Triggering Receptor Expressed on Myeloid Cells-1
0
NF-kappa B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8134Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ID : RO1 ARO46786
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ID : 2R37-ARO54780
Informations de copyright
© 2024. The Author(s).
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