title: Suppression of lymphoma and epithelial malignancies effected by interferon gamma.
abstract: The immunosurveillance of transformed cells by the immune system remains one of the most controversial and poorly understood areas of immunity. Gene-targeted mice have greatly aided our understanding of the key effector molecules in tumor immunity. Herein, we describe spontaneous tumor development in gene-targeted mice lacking interferon (IFN)-gamma and/or perforin (pfp), or the immunoregulatory cytokines, interleukin (IL)-12, IL-18, and tumor necrosis factor (TNF). Both IFN-gamma and pfp were critical for suppression of lymphomagenesis, however the level of protection afforded by IFN-gamma was strain specific. Lymphomas arising in IFN-gamma-deficient mice were very nonimmunogenic compared with those derived from pfp-deficient mice, suggesting a comparatively weaker immunoselection pressure by IFN-gamma. Single loss of IL-12, IL-18, or TNF was not sufficient for spontaneous tumor development. A significant incidence of late onset adenocarcinoma observed in both IFN-gamma- and pfp-deficient mice indicated that some epithelial tissues were also subject to immunosurveillance.
authors.affiliation: Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 8006, Australia.
authors.forename: Shayna E A
authors.initials: SE
authors.lastname: Street
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Trapani
authors.forename: Duncan
authors.initials: D
authors.lastname: MacGregor
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology*; D000375:Aging; D000818:Animals; D005434:Flow Cytometry; D018390:Gene Targeting; D007157:Immunologic Surveillance / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics; D008175:Lung Neoplasms / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012509:Sarcoma / Q000276:immunology*; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics
chemical_list: D020382:Interleukin-18; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D018664:Interleukin-12; D007371:Interferon-gamma