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.
©2013 AACR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arginase / genetics
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Arginase / metabolism
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Blotting, Western
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CD11b Antigen / genetics
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CD11b Antigen / metabolism
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Cell Differentiation
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Cell Proliferation
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Flow Cytometry
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
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Humans
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Immunologic Surveillance
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Killer Cells, Natural / pathology
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Lymphocytes, Tumor-Infiltrating / immunology*
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Lymphocytes, Tumor-Infiltrating / metabolism
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Lymphocytes, Tumor-Infiltrating / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Myeloid Cells / immunology*
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Myeloid Cells / metabolism
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Myeloid Cells / pathology
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Neoplasms / immunology*
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Neoplasms / metabolism
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Neoplasms / pathology
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Nitric Oxide / metabolism
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RNA, Messenger / genetics
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Reactive Oxygen Species / metabolism
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Microenvironment*
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
Substances
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CD11b Antigen
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RNA, Messenger
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Reactive Oxygen Species
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Tumor Necrosis Factor Receptor Superfamily, Member 7
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Nitric Oxide
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Granulocyte-Macrophage Colony-Stimulating Factor
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Arg1 protein, mouse
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Arginase