Details

Autor(en) / Beteiligte

• URDINGUIO, Rocio G
• FERNANDEZ, Agustin F
• RODRIGO, Luis
• SANTACANA, Maria
• MATIAS-GUIU, Xavier
• SOLDEVILLA, Beatriz
• DOMINGUEZ, Gemma
• BONILLA, Felix
• CAL, Santiago
• LOPEZ-OTIN, Carlos
• FRAGA, Mario F
• MONCADA-PAZOS, Angela
• HUIDOBRO, Covadonga
• RODRIGUEZ, Ramon M
• FERRERO, Cecilia
• MARTINEZ-CAMBLOR, Pablo
• OBAYA, Alvaro J
• BERNAL, Teresa
• PARRA-BLANCO, Adolfo

Titel

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

Ist Teil von

• Cancer research (Chicago, Ill.), 2013, Vol.73 (1), p.395-405

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.