title: Tumor microenvironmental conversion of natural killer cells into myeloid-derived suppressor cells.
abstract: How myeloid-derived suppressor cells (MDSC) emerge in the tumor environment remains unclear. Here, we report that GM-CSF can convert natural killer (NK) cells into MDSCs. When transferred into tumor-bearing mice, adoptively transferred NK cells lost their NK phenotype and were converted into Ly6C(high)Ly6G(high) MDSC. This conversion was abolished by exposure to IL-2 either in vitro or in vivo. Notably, we found that of the 4 maturation stages based on CD11b/CD27 expression levels, only the CD11b(high)CD27(high) NK cells could be converted into CD11b(+)Gr1(+) MDSC ex vivo. Transfer of CD27(high) NK cells from tumor-bearing mice into tumor-bearing recipients was associated with conversion to MDSC in a manner associated with reduced numbers of CD11b(high)CD27(high) and CD11b(high)CD27(low) NK cell populations in the recipients. Our results identify a pathway of MDSC development from immature NK cells in tumor-bearing hosts, providing new insights into how tumor cells modulate their host immune microenvironment to escape immune surveillance.
authors.affiliation: Authors' Affiliations: Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy; WCU, Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University; Neonatal Vaccinology Section, International Vaccine Institute, SNU Research Park; and Laboratory of Microbiology and Immunology, College of Pharmacy, Inje University, Gimhae, Gyungnam, Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Park
authors.forename: Boyeong
authors.initials: B
authors.lastname: Song
authors.forename: Yun-Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Lee
authors.forename: Ga-Eun
authors.initials: GE
authors.lastname: Lee
authors.forename: Jae-Ouk
authors.initials: JO
authors.lastname: Kim
authors.forename: Yeon-Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Chang
authors.forename: Chang-Yuil
authors.initials: CY
authors.lastname: Kang
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007157:Immunologic Surveillance; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059016:Tumor Microenvironment; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C544448:Arg1 protein, mouse; D001119:Arginase