1. Department of Pathology and Immunology, Center for Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
2. Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA

Correspondence to: Robert D. Schreiber¹ Correspondence and requests for materials should be addressed to R.D.S. (e-mail: Email: schreiber@immunology.wustl.edu).

Abstract

Lymphocytes were originally thought to form the basis of a 'cancer immunosurveillance' process that protects immunocompetent hosts against primary tumour development^{1, 2}, but this idea was largely abandoned when no differences in primary tumour development were found between athymic nude mice and syngeneic wild-type mice^{3, 4, 5}. However, subsequent observations that nude mice do not completely lack functional T cells^{6, 7} and that two components of the immune system—IFN^{8, 9} and perforin^{10, 11, 12}—help to prevent tumour formation in mice have led to renewed interest in a tumour-suppressor role for the immune response. Here we show that lymphocytes and IFN collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas and also to select for tumour cells with reduced immunogenicity. The immune response thus functions as an effective extrinsic tumour-suppressor system. However, this process also leads to the immunoselection of tumour cells that are more capable of surviving in an immunocompetent host, which explains the apparent paradox of tumour formation in immunologically intact individuals.