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Cancer Res. 2013 Jan 1;73(1):395-405. doi: 10.1158/0008-5472.CAN-12-0806. Epub 2012 Oct 29.

Immune-dependent and independent antitumor activity of GM-CSF aberrantly expressed by mouse and human colorectal tumors.

Author information

1
Cancer Epigenetics Laboratory, HUCA, Institute of Oncology of Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF2) is a cytokine produced in the hematologic compartment that may enhance antitumor immune responses, mainly by activation of dendritic cells. Here, we show that more than one-third of human colorectal tumors exhibit aberrant DNA demethylation of the GM-CSF promoter and overexpress the cytokine. Mouse engraftment experiments with autologous and homologous colon tumors engineered to repress the ectopic secretion of GM-CSF revealed the tumor-secreted GM-CSF to have an immune-associated antitumor effect. Unexpectedly, an immune-independent antitumor effect was observed that depended on the ectopic expression of GM-CSF receptor subunits by tumors. Cancer cells expressing GM-CSF and its receptor did not develop into tumors when autografted into immunocompetent mice. Similarly, 100% of the patients with human colon tumors that overexpressed GM-CSF and its receptor subunits survived at least 5 years after diagnosis. These data suggest that expression of GM-CSF and its receptor subunits by colon tumors may be a useful marker for prognosis as well as for patient stratification in cancer immunotherapy.

PMID:
23108143
DOI:
10.1158/0008-5472.CAN-12-0806
[Indexed for MEDLINE]
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