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  • Title: Distinct Populations of Immune-Suppressive Macrophages Differentiate from Monocytic Myeloid-Derived Suppressor Cells in Cancer.
    Author: Kwak T, Wang F, Deng H, Condamine T, Kumar V, Perego M, Kossenkov A, Montaner LJ, Xu X, Xu W, Zheng C, Schuchter LM, Amaravadi RK, Mitchell TC, Karakousis GC, Mulligan C, Nam B, Masters G, Hockstein N, Bennett J, Nefedova Y, Gabrilovich DI.
    Journal: Cell Rep; 2020 Dec 29; 33(13):108571. PubMed ID: 33378668.
    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.
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