Anti-G-CSF treatment induces protective tumor immunity in mouse colon cancer by promoting protective NK cell, macrophage and T cell responses
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Katherine T. Morris1, Eliseo F. Castillo2, Anita L. Ray2, Lea L. Weston2, Robert A. Nofchissey2, Joshua A. Hanson3, Von G. Samedi3, Irina V. Pinchuk4, Laurie G. Hudson5, Ellen J. Beswick2
1Department of Surgery, University of New Mexico, Albuquerque, New Mexico, USA
2Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico, USA
3Department of Pathology, University of New Mexico, Albuquerque, New Mexico, USA
4Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
5Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, New Mexico, USA
Ellen J. Beswick, e-mail: firstname.lastname@example.org
Keywords: G-CSF, colorectal cancer, NK cells, macrophages, Th1
Received: April 03, 2015 Accepted: May 21, 2015 Published: June 04, 2015
Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is highly expressed in human and mouse colorectal cancers (CRC). We previously reported that G-CSF stimulated human CRC cell growth and migration, therefore in this study we sought to examine the therapeutic potential of anti-G-CSF treatment for CRC. G-CSF is known to mobilize neutrophils, however its impact on other immune cells has not been well examined. Here, we investigated the effects of therapeutic anti-G-CSF treatment on CRC growth and anti-tumor immune responses. C57BL/6 mice treated with azoxymethane/dextran sodium sulfate (AOM/DSS) to induce neoplasms were administered anti-G-CSF or isotype control antibodies three times a week for three weeks. Animals treated with anti-G-CSF antibodies had a marked decrease in neoplasm number and size compared to the isotype control group. Colon neutrophil and macrophage frequency were unchanged, but the number of macrophages producing IL-10 were decreased while IL-12 producing macrophages were increased. NK cells were substantially increased in colons of anti-G-CSF treated mice, along with IFNγ producing CD4+ and CD8+ T cells. These studies are the first to indicate a crucial role for G-CSF inhibition in promoting protective anti-tumor immunity, and suggest that anti-G-CSF treatment is a potential therapeutic approach for CRC.
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