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Distinct Populations of Immune-Suppressive Macrophages Differentiate from Monocytic Myeloid-Derived Suppressor Cells in Cancer.
- Source :
-
Cell reports [Cell Rep] 2020 Dec 29; Vol. 33 (13), pp. 108571. - Publication Year :
- 2020
-
Abstract
- 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.<br />Competing Interests: Declaration of Interests D.I.G. is a current employee of AstraZeneca.<br /> (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Animals
CCAAT-Enhancer-Binding Proteins genetics
Cell Line, Tumor
Female
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microarray Analysis
Middle Aged
Myeloid-Derived Suppressor Cells immunology
Tumor Microenvironment
CCAAT-Enhancer-Binding Proteins metabolism
Calgranulin A physiology
Calgranulin B physiology
Immunosuppression Therapy
Macrophages metabolism
Monocytes metabolism
Myeloid-Derived Suppressor Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 33
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 33378668
- Full Text :
- https://doi.org/10.1016/j.celrep.2020.108571