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The adaptive immune response to sporadic cancer

Official URL:https://doi.org/10.1111/j.1600-065X.2007.00578.x
PubMed:View item in PubMed
Creators Name:Willimsky, G. and Blankenstein, T.
Journal Title:Immunological Reviews
Journal Abbreviation:Immunol Rev
Volume:220
Number:1
Page Range:102-112
Date:December 2007
Keywords:Sporadic Cancer, Immunosurveillance, Tolerance, Rejection Antigen, Cytotoxic T Lymphocytes, Antibodies, Animals, Mice
Abstract:Most of the current experimental cancer models do not reflect the pathophysiology of real-life cancer. Cancer usually occurs sporadically and is clonal in origin. Between tumor initiation and progression, clinically unapparent pre-malignant cells may persist for years or decades in humans. Recently, mouse models of sporadic cancer have been developed. The mouse germ-line can be engineered with high precision so that defined genes can be switched on and off in the adult organism in a targeted manner. Analysis of the immune response against sporadic tumors requires the knowledge of a tumor antigen. Ideally, a silent oncogene, for which the mice are not tolerant, is stochastically activated in individual cells. This approach offers the opportunity to analyze the adaptive immune response throughout the long process of malignant transformation and most closely resembles cancer in humans. In such a model with the highly immunogenic SV40 large T antigen as a dormant oncogene, we discovered that sporadic cancer is recognized by the adaptive immune system at the pre-malignant stage, concomitant with the induction of tumor antigen-specific tolerance. These results demonstrated that even highly immunogenic sporadic tumors are unable to induce functional cytotoxic T lymphocytes. Based on this model, we conclude that immunosurveillance plays little or no role against sporadic cancer and that tumors must not escape immune recognition or destruction.
ISSN:0105-2896
Publisher:Blackwell Publishing (U.K.)
Additional Information:The definitive version is available at www.blackwell-synergy.com
Item Type:Review

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