Distinct Populations of Immune-Suppressive Macrophages Differentiate from Monocytic Myeloid-Derived Suppressor Cells in Cancer
Copyright policy )Distinct Populations of Immune-Suppressive Macrophages Differentiate from Monocytic Myeloid-Derived Suppressor Cells in Cancer
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.
- WISTAR INSTITUTE
- Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania United States
- The Wistar Institute United States
- AstraZeneca (United Kingdom) United Kingdom
- AstraZeneca (United States) United States
Adult, Aged, 80 and over, Immunosuppression Therapy, Male, Mice, Knockout, Macrophages, Myeloid-Derived Suppressor Cells, Middle Aged, Microarray Analysis, Article, Monocytes, Mice, Inbred C57BL, Mice, Cell Line, Tumor, CCAAT-Enhancer-Binding Proteins, Animals, Calgranulin B, Humans, Calgranulin A, Female, Aged
Adult, Aged, 80 and over, Immunosuppression Therapy, Male, Mice, Knockout, Macrophages, Myeloid-Derived Suppressor Cells, Middle Aged, Microarray Analysis, Article, Monocytes, Mice, Inbred C57BL, Mice, Cell Line, Tumor, CCAAT-Enhancer-Binding Proteins, Animals, Calgranulin B, Humans, Calgranulin A, Female, Aged
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).152 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!