Here, we report that functional heterogeneity of macrophages in cancer could be determined by the nature of their precursors: monocytes (Mons) and monocytic myeloid-derived suppressor cells (M-MDSCs). Macrophages that are differentiated from M-MDSCs, but not from Mons, are immune suppressive, with a genomic profile matching that of M-MDSCs. Immune-suppressive activity of M-MDSC-derived macrophages is dependent on the persistent expression of S100A9 protein in these cells. S100A9 also promotes M2 polarization of macrophages. Tissue-resident- and Mon-derived macrophages lack expression of this protein. S100A9-dependent immune-suppressive activity of macrophages involves transcription factor C/EBPβ. The presence of S100A9-positive macrophages in tumor tissues is associated with shorter survival in patients with head and neck cancer and poor response to PD-1 antibody treatment in patients with metastatic melanoma. Thus, this study reveals the pathway of the development of immune-suppressive macrophages and suggests an approach to their selective targeting.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809772 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2020.108571 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ETV5-Mediated Transcriptional Repression of DDIT4 Blocks Macrophage Pro-Inflammatory Activation in Diabetic Atherosclerosis.
Cardiovasc Toxicol
January 2025
Department of Cadre Ward, The First Affiliated Hospital of Harbin Medical University, No. 23, Postal Street, Harbin, 150001, Heilongjiang, PR China.
Atherosclerosis risk is elevated in diabetic patients, but the underlying mechanism such as the involvement of macrophages remains unclear. Here, we investigated the underlying mechanism related to the pro-inflammatory activation of macrophages in the development of diabetic atherosclerosis. Bioinformatics tools were used to analyze the macrophage-related transcriptome differences in patients with atherosclerosis and diabetic mice.
View Article and Find Full Text PDFArginine metabolism in myeloid cells in health and disease.
Semin Immunopathol
January 2025
Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
Metabolic flexibility is key for the function of myeloid cells. Arginine metabolism is integral to the regulation of myeloid cell responses. Nitric oxide (NO) production from arginine is vital for the antimicrobial and pro-inflammatory responses.
View Article and Find Full Text PDFA safe haven for cancer cells: tumor plus stroma control by DYRK1B.
Oncogene
January 2025
Department of Gastroenterology, Endocrinology and Metabolism, Center for Tumor and Immune Biology, Philipps University Marburg, Marburg, Germany.
The development of resistance remains one of the biggest challenges in clinical cancer patient care and it comprises all treatment modalities from chemotherapy to targeted or immune therapy. In solid malignancies, drug resistance is the result of adaptive processes occurring in cancer cells or the surrounding tumor microenvironment (TME). Future therapy attempts will therefore benefit from targeting both, tumor and stroma compartments and drug targets which affect both sides will be highly appreciated.
View Article and Find Full Text PDFsVEGFR3 alleviates myocardial ischemia/reperfusion injury through regulating mitochondrial homeostasis and immune cell infiltration.
Apoptosis
January 2025
Department of Cardiac Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Rd, Guangzhou, 510080, China.
Recent studies have suggested that sVEGFR3 is involved in cardiac diseases by regulating lymphangiogenesis; however, results are inconsistent. The aim of this study was to investigate the function and mechanism of sVEGFR3 in myocardial ischemia/reperfusion injury (MI/RI). sVEGFR3 effects were evaluated in vivo in mice subjected to MI/RI, and in vitro using HL-1 cells exposed to oxygen-glucose deprivation/reperfusion.
View Article and Find Full Text PDFFluid flow impacts endothelial-monocyte interactions in a model of vascular inflammatory fibrosis.
Sci Rep
January 2025
Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA.
The aberrant vascular response associated with tendon injury results in circulating immune cell infiltration and a chronic inflammatory feedback loop leading to poor healing outcomes. Studying this dysregulated tendon repair response in human pathophysiology has been historically challenging due to the reliance on animal models. To address this, our group developed the human tendon-on-a-chip (hToC) to model cellular interactions in the injured tendon microenvironment; however, this model lacked the key element of physiological flow in the vascular compartment.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!