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// Katherine T. Morris 1 , Eliseo F. Castillo 2 , Anita L. Ray 2 , Lea L. Weston 2 , Robert A. Nofchissey 2 , Joshua A. Hanson 3 , Von G. Samedi 3 , Irina V. Pinchuk 4 , Laurie G. Hudson 5 , Ellen J. Beswick 2 1 Department of Surgery, University of New Mexico, Albuquerque, New Mexico, USA 2 Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico, USA 3 Department of Pathology, University of New Mexico, Albuquerque, New Mexico, USA 4 Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA 5 Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, New Mexico, USA Correspondence to: Ellen J. Beswick, e-mail: ebeswick@salud.unm.edu Keywords: G-CSF, colorectal cancer, NK cells, macrophages, Th1 Received: April 03, 2015 Accepted: May 21, 2015 Published: June 04, 2015 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.