title: Cross-talk among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors.
abstract: MDSC and macrophages are present in most solid tumors and are important drivers of immune suppression and inflammation. It is established that cross-talk between MDSC and macrophages impacts anti-tumor immunity; however, interactions between tumor cells and MDSC or macrophages are less well studied. To examine potential interactions between these cells, we studied the impact of MDSC, macrophages, and four murine tumor cell lines on each other, both in vitro and in vivo. We focused on IL-6, IL-10, IL-12, TNF-α, and NO, as these molecules are produced by macrophages, MDSC, and many tumor cells; are present in most solid tumors; and regulate inflammation. In vitro studies demonstrated that MDSC-produced IL-10 decreased macrophage IL-6 and TNF-α and increased NO. IL-6 indirectly regulated MDSC IL-10. Tumor cells increased MDSC IL-6 and vice versa. Tumor cells also increased macrophage IL-6 and NO and decreased macrophage TNF-α. Tumor cell-driven macrophage IL-6 was reduced by MDSC, and tumor cells and MDSC enhanced macrophage NO. In vivo analysis of solid tumors identified IL-6 and IL-10 as the dominant cytokines and demonstrated that these molecules were produced predominantly by stromal cells. These results suggest that inflammation within solid tumors is regulated by the ratio of tumor cells to MDSC and macrophages and that interactions of these cells have the potential to alter significantly the inflammatory milieu within the tumor microenvironment.
authors.affiliation: Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, Maryland, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Beury
authors.affiliation: Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, Maryland, USA.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Parker
authors.affiliation: Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, Maryland, USA.
authors.forename: Maeva
authors.initials: M
authors.lastname: Nyandjo
authors.affiliation: Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, Maryland, USA.
authors.forename: Pratima
authors.initials: P
authors.lastname: Sinha
authors.affiliation: Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, Maryland, USA.
authors.forename: Kayla A
authors.initials: KA
authors.lastname: Carter
authors.affiliation: Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, Maryland, USA srosenbe@umbc.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ostrand-Rosenberg
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D007249:Inflammation; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000502:physiology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014185:Transplantation, Isogeneic; D059016:Tumor Microenvironment / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: C556062:IL10 protein, mouse; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide
keywords: IL-10; IL-6; cancer; cytokines; nitric oxide; tumor microenvironment