Suppression of lymphoma and epithelial malignancies effected by interferon gamma.
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.
Street
Shayna E A
SE
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 8006, Australia.
Trapani
Joseph A
JA
MacGregor
Duncan
D
Smyth
Mark J
MJ
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
D020382:Interleukin-18; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D018664:Interleukin-12; D007371:Interferon-gamma