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Pigment Cell Melanoma Res. 2010 Oct;23(5):649-60. doi: 10.1111/j.1755-148X.2010.00744.x. Epub 2010 Jul 23.

Autochthonous primary and metastatic melanomas in Hgf-Cdk4 R24C mice evade T-cell-mediated immune surveillance.

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1
Laboratory of Experimental Dermatology, Department of Dermatology and Allergology, University of Bonn, Bonn, Germany.

Abstract

Genetically engineered mouse models offer new opportunities to investigate the role of cell-mediated immunity in the natural progression of melanoma in an immunocompetent host. Here we report that Hgf-Cdk4(R24C) mice spontaneously develop a spectrum of primary melanomas with high penetrance during their first year of life. Malignant transformation proceeds in a stepwise manner from multiple melanocytic nevi to single nodular melanomas and disseminated metastases in most mice. Migrating melanoma cells invade the draining lymph nodes without activating the immune system. Autochthonous primary tumors are destroyed following experimental introduction of immune surveillance using an adoptive lymphocyte transfer approach. However, some tumor cells are able to survive, evade immune cell control, and recur both locally and systemically. Immune tolerance in recurring tumors may be supported by immunosuppressive Gr1(+) myeloid cells. Taken together, our results demonstrate that primary and metastatic melanomas developing spontaneously in Hgf-Cdk4(R24C) mice effectively evade cellular immune surveillance.

[Indexed for MEDLINE]

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