Abstract
GM-CSF as an adjuvant has been shown to promote antitumor immunity in mice and humans; however, the underlying mechanism of GM-CSF-induced antitumor immunity remains incompletely understood. In this study, we demonstrate that GM-CSF potentiates the efficacy of cancer vaccines through IL9-producing Th (Th9) cells. GM-CSF selectively enhanced Th9 cell differentiation by regulating the COX2-PGE2 pathway while inhibiting the differentiation of induced regulatory T (iTreg) cells in vitro and in vivo GM-CSF-activated monocyte-derived dendritic cells converted tumor-specific naïve Th cells into Th9 cells, and delayed tumor growth by inducing antitumor CTLs in an IL9-dependent manner. Our findings reveal a mechanism for the adjuvanticity of GM-CSF and provide a rationale for the use of GM-CSF in cancer vaccines.
©2019 American Association for Cancer Research.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Animals
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Antigen-Presenting Cells / immunology
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Cancer Vaccines / immunology
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Cell Differentiation / drug effects
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Cell Line, Tumor
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Cyclooxygenase 2 / metabolism
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Dendritic Cells / immunology
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Dinoprostone / metabolism
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Disease Models, Animal
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Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Humans
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Immunotherapy
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Interleukin-9 / immunology*
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Interleukin-9 / metabolism
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Lymphocyte Activation / drug effects
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Mice
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Neoplasms / immunology*
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Neoplasms / therapy*
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Helper-Inducer / drug effects
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology
Substances
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Adjuvants, Immunologic
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Cancer Vaccines
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Interleukin-9
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Granulocyte-Macrophage Colony-Stimulating Factor
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Ptgs2 protein, mouse
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Cyclooxygenase 2
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Dinoprostone