Enzler, ThomasGillessen, SilkeManis, John P.Ferguson, DavidFleming, JamesAlt, Frederick W.Mihm, MartinDranoff, Glenn2019-10-052003Enzler, Thomas, Silke Gillessen, John P. Manis, David Ferguson, James Fleming, Frederick W. Alt, Martin Mihm, and Glenn Dranoff. 2003. “Deficiencies of GM-CSF and Interferon γ Link Inflammation and Cancer.” The Journal of Experimental Medicine 197 (9): 1213–19. https://doi.org/10.1084/jem.20021258.0022-10071540-9538http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483363Chronic 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.en-USJournal Article2019-10-0510.1084/jem.20021258