Distinct Populations of Immune-Suppressive Macrophages Differentiate from Monocytic Myeloid-Derived Suppressor Cells in Cancer.

Autor:	Kwak T; The Wistar Institute, Philadelphia, PA 19104, USA., Wang F; The Wistar Institute, Philadelphia, PA 19104, USA., Deng H; The Wistar Institute, Philadelphia, PA 19104, USA., Condamine T; The Wistar Institute, Philadelphia, PA 19104, USA., Kumar V; The Wistar Institute, Philadelphia, PA 19104, USA., Perego M; The Wistar Institute, Philadelphia, PA 19104, USA., Kossenkov A; The Wistar Institute, Philadelphia, PA 19104, USA., Montaner LJ; The Wistar Institute, Philadelphia, PA 19104, USA., Xu X; Tara Miller Melanoma Center, Abramson Cancer Center and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Xu W; Tara Miller Melanoma Center, Abramson Cancer Center and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Zheng C; Tara Miller Melanoma Center, Abramson Cancer Center and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Schuchter LM; Abramson Cancer Center and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Amaravadi RK; Abramson Cancer Center and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Mitchell TC; Abramson Cancer Center and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Karakousis GC; Abramson Cancer Center and Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Mulligan C; Helen F Graham Cancer Center and Research Institute, Christiana Care, Newark, DE 19713, USA., Nam B; Helen F Graham Cancer Center and Research Institute, Christiana Care, Newark, DE 19713, USA., Masters G; Helen F Graham Cancer Center and Research Institute, Christiana Care, Newark, DE 19713, USA., Hockstein N; Helen F Graham Cancer Center and Research Institute, Christiana Care, Newark, DE 19713, USA., Bennett J; Helen F Graham Cancer Center and Research Institute, Christiana Care, Newark, DE 19713, USA., Nefedova Y; The Wistar Institute, Philadelphia, PA 19104, USA., Gabrilovich DI; Cancer Immunology, AstraZeneca, Gaithersburg, MD 20878, USA. Electronic address: dmitry.gabrilovich@astrazeneca.com.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Dec 29; Vol. 33 (13), pp. 108571.
DOI:	10.1016/j.celrep.2020.108571
Abstrakt:	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. Competing Interests: Declaration of Interests D.I.G. is a current employee of AstraZeneca. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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