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Characterizing Macrophage Diversity in Metastasis-Bearing Lungs Reveals a Lipid-Associated Macrophage Subset
- Source :
- Cancer Res
- Publication Year :
- 2021
- Publisher :
- American Association for Cancer Research (AACR), 2021.
-
Abstract
- While macrophages are among the most abundant immune cell type found within primary and metastatic mammary tumors, how their complexity and heterogeneity change with metastatic progression remains unknown. Here, macrophages were isolated from the lungs of mice bearing orthotopic mammary tumors for single-cell RNA sequencing (scRNA-seq). Seven distinct macrophage clusters were identified, including populations exhibiting enhanced differential expression of genes related to antigen presentation (H2-Aa, Cd74), cell cycle (Stmn1, Cdk1), and interferon signaling (Isg15, Ifitm3). Interestingly, one cluster demonstrated a profile concordant with lipid-associated macrophages (Lgals3, Trem2). Compared with nontumor-bearing controls, the number of these cells per gram of tissue was significantly increased in lungs from tumor-bearing mice, with the vast majority costaining positively with the alveolar macrophage marker Siglec-F. Enrichment of genes implicated in pathways related to lipid metabolism as well extracellular matrix remodeling and immunosuppression was observed. In addition, these cells displayed reduced capacity for phagocytosis. Collectively, these findings highlight the diversity of macrophages present within metastatic lesions and characterize a lipid-associated macrophage subset previously unidentified in lung metastases. Significance: scRNA-seq of macrophages isolated from lung metastases reveals extensive macrophage heterogeneity and identifies a novel subpopulation enriched for genes involved in lipid metabolism, extracellular matrix remodeling, and immunosuppression.
- Subjects :
- Cancer Research
Lung Neoplasms
CD74
Antigen presentation
Mice, Nude
Apoptosis
Breast Neoplasms
Biology
Article
Extracellular Vesicles
Mice
Immune system
Interferon
Biomarkers, Tumor
Tumor Cells, Cultured
medicine
Animals
Humans
Macrophage
RNA-Seq
Cell Proliferation
Immunosuppression Therapy
Mice, Inbred BALB C
Tumor microenvironment
Macrophages
Lipid metabolism
Lipids
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
Oncology
Alveolar macrophage
Cancer research
Female
medicine.drug
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 81
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....c660aceef5ca223b2b4f2ca92b842c61