Characterizing Macrophage Diversity in Metastasis-Bearing Lungs Reveals a Lipid-Associated Macrophage Subset.

Autor:	Huggins DN; Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota., LaRue RS; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota., Wang Y; Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota., Knutson TP; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota., Xu Y; Department of Integrative Biology and Physiology, Medical School, University of Minnesota, Minneapolis, Minnesota., Williams JW; Department of Integrative Biology and Physiology, Medical School, University of Minnesota, Minneapolis, Minnesota.; Center for Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota., Schwertfeger KL; Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota. schwe251@umn.edu.; Center for Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota.; Masonic Cancer Center, Office of Academic Clinical Affairs, University of Minnesota, Minneapolis, Minnesota.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2021 Oct 15; Vol. 81 (20), pp. 5284-5295. Date of Electronic Publication: 2021 Aug 13.
DOI:	10.1158/0008-5472.CAN-21-0101
Abstrakt:	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. (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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