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GM-CSF Promotes Antitumor Immunity by Inducing Th9 Cell Responses.
- Source :
-
Cancer immunology research [Cancer Immunol Res] 2019 Mar; Vol. 7 (3), pp. 498-509. Date of Electronic Publication: 2019 Feb 06. - Publication Year :
- 2019
-
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-PGE <subscript>2</subscript> 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.<br /> (©2019 American Association for Cancer Research.)
- Subjects :
- Adjuvants, Immunologic pharmacology
Animals
Antigen-Presenting Cells immunology
Cancer Vaccines immunology
Cell Differentiation drug effects
Cell Line, Tumor
Cyclooxygenase 2 metabolism
Dendritic Cells immunology
Dinoprostone metabolism
Disease Models, Animal
Granulocyte-Macrophage Colony-Stimulating Factor pharmacology
Humans
Immunotherapy
Interleukin-9 metabolism
Lymphocyte Activation drug effects
Mice
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Helper-Inducer drug effects
T-Lymphocytes, Helper-Inducer metabolism
T-Lymphocytes, Regulatory drug effects
T-Lymphocytes, Regulatory immunology
Granulocyte-Macrophage Colony-Stimulating Factor immunology
Interleukin-9 immunology
Neoplasms immunology
Neoplasms therapy
T-Lymphocytes, Helper-Inducer immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2326-6074
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer immunology research
- Publication Type :
- Academic Journal
- Accession number :
- 30728152
- Full Text :
- https://doi.org/10.1158/2326-6066.CIR-18-0518