Deficiencies of GM-CSF and interferon gamma link inflammation and cancer.
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.
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Thomas
T
Enzler
Silke
S
Gillessen
John P
JP
Manis
David
D
Ferguson
James
J
Fleming
Frederick W
FW
Alt
Martin
M
Mihm
Glenn
G
Dranoff
D000818:Animals; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000503:physiopathology*
D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor