Immunogenicity of premalignant lesions is the primary cause of general cytotoxic T lymphocyte unresponsiveness

Willimsky, Gerald; Czéh, Melinda; Loddenkemper, Christoph; Gellermann, Johanna; Schmidt, Karin; Wust, Peter; Stein, Harald; Blankenstein, Thomas

doi:10.1084/jem.20072016

Cited by 99 publications

(118 citation statements)

References 61 publications

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“…A major goal of these studies should be to narrow the predicted range of sarcoma formation at individual 3-MCA doses (Figure 1), such that comparisons between immunocompetent and immunodeficient mice may be validated. Given the importance of tumour-specific or -associated antigens in the generation of antitumour immune responses, these studies should also be performed using a system where antigens may be defined and tracked throughout the development of spontaneous or chemically induced tumours, techniques for which have been described (Willimsky et al, 2008). The criteria for categorising 'tumour-free' mice must also be clarified.…”

Section: Refining the Immunoediting Hypothesismentioning

confidence: 99%

A critical analysis of the tumour immunosurveillance controversy for 3-MCA-induced sarcomas

Schreiber

Podack

2009

Br J Cancer

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The cancer immunoediting hypothesis has gained significant footing over the past decade as a result of work performed using sarcomas induced by 3-methylcholanthrene (3-MCA) in mice. Despite the progress made by several groups in establishing evidence for the three phases of immunoediting (elimination, equilibrium and escape), there continues to be active controversy on the nature of interaction between spontaneously formed tumour cells and the immune system during the early phases of tumourigenesis. At the root of this controversy is conflicting and unresolved evidence spanning back to the 1970s regarding the incidence and frequency of 3-MCA-induced sarcomas in immunocompetent mice as compared to immunodeficient mice. In this mini review we provide a critical analysis of both sides of this controversy.

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Section: Refining the Immunoediting Hypothesismentioning

confidence: 99%

A critical analysis of the tumour immunosurveillance controversy for 3-MCA-induced sarcomas

Schreiber

Podack

2009

Br J Cancer

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“…In humans, tumor-infiltrating lymphocytes of colon carcinoma have been correlated with a favorable prognosis (Page`s et al, 2010). However, tumor-infiltrating lymphocytes were also abundantly detected in premalignant lesions of LoxP-Tag mice that had acquired Tag-specific CTL tolerance (Willimsky et al, 2008). Therefore, it remains to be shown whether the tumor-infiltrating lymphocytes reflect a tumor-promoting inflammatory response rather than a tumoricidal response.…”

Section: Sporadic Colorectal Cancer Modelmentioning

confidence: 99%

The immune response to sporadic colorectal cancer in a novel mouse model

et al. 2010

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Current mouse models do not reflect the sporadic nature of colon cancer and do not allow the analysis of antitumor immune response because of the lack of known tumorspecific antigens. Two transgenic mouse models with spontaneous tumor development were generated, directing the expression of SV40T antigen (Tag) either constitutively (Vil-Cre Â LoxP-Tag-transgenic mice) or stochastically (Vil-Cre-ER T2 Â LoxP-Tag-transgenic mice) into the putative stem cell region of the crypt of Lieberku¨hn. Tumor development and antitumor immune response were monitored. Vil-Cre Â LoxP-Tag mice developed multiple adenocarcinomas of the small intestine and colon at an average age of 6 months. During the tumor development, Tag-specific immunoglobulin G (IgG) antibodies were induced in half of the mice, although they had developed neonatal cytotoxic T lymphocyte (CTL) tolerance. This model shows similarity to hereditary colon cancer but not to the sporadic tumor development. Therefore, the conditional Vil-Cre-ER T2 Â LoxP-Tag mice were established, in which expression of the dormant Tag was induced by stochastic, tissue-specific activation of Cre recombinase. These mice spontaneously developed highly invasive, metastasizing colon carcinomas at an average age of 20 months. Colon carcinomas expressed epithelial and/or neuroendocrine markers depending on the grade of differentiation. Young Vil-Cre-ER T2 Â LoxP-Tag mice had retained CTL responses against epitope IV of Tag. The tumors induced strong anti-Tag IgG responses. We report, for the first time, a mouse model based on stochastic, tissue-specific activation of a dormant oncogene in the colon allowing the analysis of antitumor immune response against primary colorectal cancer.

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“…Some studies suggested that tumor cells induce local immune-tolerance during tumor progression (Willimsky et al, 2008). The major determinant of the poor outcome of immunotherapy may be the immune suppression within the tumor microenvironment (Gabrilovich et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The tumor immunosuppressive microenvironment impairs the therapy of anti-HER2/neu antibody

Liu

et al. 2012

Protein Cell

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Immunogenicity of premalignant lesions is the primary cause of general cytotoxic T lymphocyte unresponsiveness

Cited by 99 publications

References 61 publications

A critical analysis of the tumour immunosurveillance controversy for 3-MCA-induced sarcomas

A critical analysis of the tumour immunosurveillance controversy for 3-MCA-induced sarcomas

The immune response to sporadic colorectal cancer in a novel mouse model

The tumor immunosuppressive microenvironment impairs the therapy of anti-HER2/neu antibody

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