Publication
Deficiencies of GM-CSF and interferon gamma link inflammation and cancer
Journal Paper/Review - May 5, 2003
Enzler Thomas, Gillessen Sommer Silke, Manis John P, Ferguson David, Fleming James, Alt Frederick W, Mihm Martin, Dranoff Glenn
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PubMed
Doi
Citation
Type
Journal
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Issn Print
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Brief description/objective
Chronic inflammation contributes to carcinogenesis, but the underlying mechanisms are poorly understood. We report that aged granulocyte-macrophage colony stimulating factor (GM-CSF)-deficient mice develop a systemic lupus erythematosis (SLE)-like disorder associated with the impaired phagocytosis of apoptotic cells. Concurrent deficiency of interferon (IFN)-gamma attenuates the SLE, but promotes the formation of diverse hematologic and solid neoplasms within a background of persistent infection and inflammation. Whereas activated B cells show a resistance to fas-induced apoptosis, antimicrobial therapy prevents lymphomagenesis and solid tumor development. These findings demonstrate that the interplay of infectious agents with cytokine-mediated regulation of immune homeostasis is a critical determinant of cancer susceptibility.