Open AccessJournal Article
Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T-CELL suppressive activity
Kiavash Movahedi,Martin Guiliams,Jan Van den Bossche,Rafael Van den Bergh,Conny Gysemans,Alain Beschin,Patrick De Baetselier,Jo A. Van Ginderachter +7 more
TLDR
This work identified 2 distinct MDSC subfractions with clear morphologic, molecular, and functional differences, and refined tumor-induced MDSCs functions by uncovering mechanistically distinct M DSC subpopulations, potentially relevant for MDSc-targeted therapies.Abstract:
The induction of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) is an important immune-evading mechanism used by tumors. However, the exact nature and function of MDSCs remain elusive, especially because they constitute a heterogeneous population that has not yet been clearly defined. Here, we identified 2 distinct MDSC subfractions with clear morphologic, molecular, and functional differences. These fractions consisted of either mononuclear cells (MO-MDSCs), resembling inflammatory monocytes, or low-density polymorphonuclear cells (PMN-MDSCs), akin to immature neutrophils. Interestingly, both MO-MDSCs and PMN-MDSCs suppressed antigen-specific T-cell responses, albeit using distinct effector molecules and signaling pathways. Blocking IFN-gamma or disrupting STAT1 partially impaired suppression by MO-MDSCs, for which nitric oxide (NO) was one of the mediators. In contrast, while IFN-gamma was strictly required for the suppressor function of PMN-MDSCs, this did not rely on STAT1 signaling or NO production. Finally, MO-MDSCs were shown to be potential precursors of highly antiproliferative NO-producing mature macrophages. However, distinct tumors differentially regulated this inherent MO-MDSC differentiation program, indicating that this phenomenon was tumor driven. Overall, our data refine tumor-induced MDSC functions by uncovering mechanistically distinct MDSC subpopulations, potentially relevant for MDSC-targeted therapies.read more
Citations
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Myeloid-derived suppressor cells as regulators of the immune system.
TL;DR: The origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit are discussed.
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Coordinated regulation of myeloid cells by tumours
TL;DR: This work considers myeloid cells as an intricately connected, complex, single system and focuses on how tumours manipulate the myeloids system to evade the host immune response.
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Development of Monocytes, Macrophages, and Dendritic Cells
TL;DR: The current understanding of myeloid lineage development is reviewed and the developmental pathways and cues that drive differentiation are described, which are central to the development of immunologic memory and tolerance in mice.
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Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: “N1” versus “N2” TAN
Zvi G. Fridlender,Jing Sun,Samuel Kim,Veena Kapoor,Guanjun Cheng,Leona E. Ling,G. Scott Worthen,Steven M. Albelda +7 more
TL;DR: It is suggested that TGF-beta within the tumor microenvironment induces a population of TAN with a protumor phenotype, and depletion of these neutrophils significantly blunts antitumor effects of treatment and reduces CD8(+) T cell activation.
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Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards
Vincenzo Bronte,Sven Brandau,Shu Hsia Chen,Mario P. Colombo,Alan B. Frey,Tim F. Greten,Susanna Mandruzzato,Peter J. Murray,Augusto C. Ochoa,Suzanne Ostrand-Rosenberg,Paulo C. Rodriguez,Antonio Sica,Viktor Umansky,Viktor Umansky,Robert H. Vonderheide,Dmitry I. Gabrilovich +15 more
TL;DR: The authors identify the challenges and proposed set of minimal reporting guidelines for mouse and human MDSC are a heterogeneous population expanded in cancer and other chronic inflammatory conditions.
References
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Journal ArticleDOI
Myeloid-derived suppressor cells as regulators of the immune system.
TL;DR: The origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit are discussed.
Journal ArticleDOI
Blood Monocytes Consist of Two Principal Subsets with Distinct Migratory Properties
TL;DR: Using a murine adoptive transfer system to probe monocyte homing and differentiation in vivo, two functional subsets among murine blood monocytes are identified: a short-lived CX(3)CR1(lo)CCR2(+)Gr1(+) subset that is actively recruited to inflamed tissues and a CX (3) CR1(hi)CCS1-dependent recruitment to noninflamed tissues.
Journal ArticleDOI
Coordinated regulation of myeloid cells by tumours
TL;DR: This work considers myeloid cells as an intricately connected, complex, single system and focuses on how tumours manipulate the myeloids system to evade the host immune response.
Journal ArticleDOI
Development of Monocytes, Macrophages, and Dendritic Cells
TL;DR: The current understanding of myeloid lineage development is reviewed and the developmental pathways and cues that drive differentiation are described, which are central to the development of immunologic memory and tolerance in mice.
Journal ArticleDOI
Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: “N1” versus “N2” TAN
Zvi G. Fridlender,Jing Sun,Samuel Kim,Veena Kapoor,Guanjun Cheng,Leona E. Ling,G. Scott Worthen,Steven M. Albelda +7 more
TL;DR: It is suggested that TGF-beta within the tumor microenvironment induces a population of TAN with a protumor phenotype, and depletion of these neutrophils significantly blunts antitumor effects of treatment and reduces CD8(+) T cell activation.