The Journal of Experimental Medicine
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Published 1 July 2002. doi:10.1084/jem.20020063
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© Rockefeller University Press, 0022-1007/2002/7/129/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 1, July 1, 2002 129-134

Brief Definitive Report

Suppression of Lymphoma and Epithelial Malignancies Effected by Interferon {gamma}

Shayna E.A. Street1, Joseph A. Trapani1, Duncan MacGregor2 and Mark J. Smyth1

1 Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 8006, Australia
2 Department of Anatomical Pathology, Austin and Repatriation Medical Centre, Heidelberg 3084, Australia

Address correspondence to M.J. Smyth, Cancer Immunology, St. Andrews Place, East Melbourne, Victoria 3002, Australia. Phone: 61-3-9656-3728; Fax: 61-3-9656-1411; E-mail: m.smyth{at}pmci.unimelb.edu.au

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.

Key Words: immunosurveillance • effector • interferon • lymphoma • adenocarcinoma


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