Immune-Dependent and Independent Antitumor Activity of GM-CSF Aberrantly Expressed by Mouse and Human Colorectal Tumors

• DOI: 10.1158/0008-5472.can-12-0806
• Publication Date: 2012-10-30T05:49:58Z
• Authors: Rocio G. Urdinguio; Agustin F. Fernandez; Angela Moncada-Pazos; Covadonga Huidobro; Ramon M. Rodriguez; Cecilia Ferrero; Pablo Martinez-Ca...; Alvaro J. Obaya; Teresa Bernal; Adolfo Parra-Blanco; Luis Rodrigo; Maria Santacana; Xavier Matias-Guiu; Beatriz Soldevilla; Gemma Dominguez; Felix Bonilla; Santiago Cal; Carlos Lopez-Otin; Mario F. Fraga
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Granulocyte-Macrophage Colony-Stimulating Factor; Mice, Nude; Enzyme-Linked Immunosorbent Assay; DNA Methylation; Prognosis; Real-Time Polymerase Chain Reaction; Transfection; Immunohistochemistry; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Tissue Array Analysis; Biomarkers, Tumor; Animals; Humans; Colorectal Neoplasms; Promoter Regions, Genetic; In Situ Hybridization

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 more than one-third human colorectal tumors exhibit aberrant DNA demethylation GM-CSF promoter and overexpress cytokine. Mouse engraftment experiments with autologous homologous colon engineered to repress ectopic secretion revealed tumor-secreted have an immune-associated effect. Unexpectedly, immune-independent effect was observed depended on expression receptor subunits tumors. Cancer cells expressing its did not develop into when autografted immunocompetent mice. Similarly, 100% patients overexpressed survived at least 5 years after diagnosis. These data suggest be useful marker for prognosis as well patient stratification cancer immunotherapy.