期刊
CANCER RESEARCH
卷 73, 期 1, 页码 395-405出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-12-0806
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类别
资金
- IUOPA
- Fundacion Cientifica de la aecc
- FIS [FI07/00380]
- Spanish Ministry of Health [PI061267, PS09/024549]
- FIS/FEDER [PI11/01728]
- ISCIII [CP11/00131]
- Spanish National Research Council (CSIC) [200820I172]
- Community of Asturias [FYCIT IB09-106]
- Obra Social Cajastur, Spain
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. Cancer Res; 73(1); 395-405. (C)2012 AACR.
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