Anti-G-CSF treatment induces protective tumor immunity in mouse colon cancer by promoting NK cell, macrophage and T cell responses

Katherine T. Morris, Eliseo F. Castillo, Anita L. Ray, Lea L. Weston, Robert A. Nofchissey, Joshua A. Hanson, Von G. Samedi, Iryna Pinchuk, Laurie G. Hudson, Ellen J. Beswick

Research output: Contribution to journalArticle

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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<sup>+</sup> and CD8<sup>+</sup> 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.

Original languageEnglish (US)
Pages (from-to)22338-22347
Number of pages10
JournalOncotarget
Volume6
Issue number26
StatePublished - 2015

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Granulocyte Colony-Stimulating Factor
Natural Killer Cells
Colonic Neoplasms
Immunity
Macrophages
T-Lymphocytes
Colorectal Neoplasms
Neoplasms
Colon
Neutrophils
Azoxymethane
Dextran Sulfate
Antibodies
Therapeutic Uses
Interleukin-12
Growth
Inbred C57BL Mouse
Interleukin-10
Cell Movement
Cytokines

Keywords

  • Colorectal cancer
  • G-CSF
  • Macrophages
  • NK cells
  • Th1

ASJC Scopus subject areas

  • Oncology

Cite this

Morris, K. T., Castillo, E. F., Ray, A. L., Weston, L. L., Nofchissey, R. A., Hanson, J. A., ... Beswick, E. J. (2015). Anti-G-CSF treatment induces protective tumor immunity in mouse colon cancer by promoting NK cell, macrophage and T cell responses. Oncotarget, 6(26), 22338-22347.

Anti-G-CSF treatment induces protective tumor immunity in mouse colon cancer by promoting NK cell, macrophage and T cell responses. / Morris, Katherine T.; Castillo, Eliseo F.; Ray, Anita L.; Weston, Lea L.; Nofchissey, Robert A.; Hanson, Joshua A.; Samedi, Von G.; Pinchuk, Iryna; Hudson, Laurie G.; Beswick, Ellen J.

In: Oncotarget, Vol. 6, No. 26, 2015, p. 22338-22347.

Research output: Contribution to journalArticle

Morris, KT, Castillo, EF, Ray, AL, Weston, LL, Nofchissey, RA, Hanson, JA, Samedi, VG, Pinchuk, I, Hudson, LG & Beswick, EJ 2015, 'Anti-G-CSF treatment induces protective tumor immunity in mouse colon cancer by promoting NK cell, macrophage and T cell responses', Oncotarget, vol. 6, no. 26, pp. 22338-22347.
Morris KT, Castillo EF, Ray AL, Weston LL, Nofchissey RA, Hanson JA et al. Anti-G-CSF treatment induces protective tumor immunity in mouse colon cancer by promoting NK cell, macrophage and T cell responses. Oncotarget. 2015;6(26):22338-22347.
Morris, Katherine T. ; Castillo, Eliseo F. ; Ray, Anita L. ; Weston, Lea L. ; Nofchissey, Robert A. ; Hanson, Joshua A. ; Samedi, Von G. ; Pinchuk, Iryna ; Hudson, Laurie G. ; Beswick, Ellen J. / Anti-G-CSF treatment induces protective tumor immunity in mouse colon cancer by promoting NK cell, macrophage and T cell responses. In: Oncotarget. 2015 ; Vol. 6, No. 26. pp. 22338-22347.
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