title: Anti-G-CSF treatment induces protective tumor immunity in mouse colon cancer by promoting protective NK cell, macrophage and T cell responses.
abstract: 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.
authors.affiliation: Department of Surgery, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Morris
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Eliseo F
authors.initials: EF
authors.lastname: Castillo
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Anita L
authors.initials: AL
authors.lastname: Ray
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Lea L
authors.initials: LL
authors.lastname: Weston
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Nofchissey
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Hanson
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Von G
authors.initials: VG
authors.lastname: Samedi
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Pinchuk
authors.affiliation: Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Laurie G
authors.initials: LG
authors.lastname: Hudson
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Beswick
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D016179:Granulocyte Colony-Stimulating Factor
keywords: G-CSF; NK cells; Th1; colorectal cancer; macrophages