Immunoproteasome subunits LMP2 and LMP7 downregulation in... : Melanoma Research (original) (raw)

ORIGINAL ARTICLES

Immunoproteasome subunits LMP2 and LMP7 downregulation in primary malignant melanoma lesions

association with lack of spontaneous regression

Dissemond, Joachima; Goette, Petraa; Moers, Janeta; Lindeke, Anettea; Goos, Manfreda; Ferrone, Soldanob; Wagner, Stephan Na

aDepartment of Dermatology, University School of Medicine, Essen, Germany, and bDepartment of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA.

Sponsorship: This work was supported by the Deutsche Forschungsgemeinschaft Grant Wa 705/4-2 and by the Public Health grant CA67988, awarded by the National Cancer Institute, Department of Health and Human Services and by the Roswell Park Cancer Center Support Grant P30 CA 16056.

Correspondence and requests for reprints to Stephan N. Wagner, Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, University of Vienna Medical School, Währinger Gürtel 18-20, 1090 Vienna, Austria. Tel: +43 1 40400 7714; fax: +43 1 403 1900; e-mail: [email protected]

Received 20 September 2002 Accepted 31 March 2003

Abstract

Recently, expression of the immunoproteasome subunits low molecular protein (LMP) 2 or LMP7 was shown to reduce the presentation of certain major histocompatibility complex (MHC) class I-restricted tumour peptide epitopes in renal cell carcinoma and melanoma cells. This may provide the tumour cells with an immune escape mechanism. To test the relevance of this hypothesis, we have taken advantage of the fact that spontaneous regression of human primary melanoma is thought to be the result of a successful peptide-specific cellular immune response in vivo. Immunohistochemical staining with anti-LMP2 and anti-LMP7 xenoantibodies showed a significantly higher expression of these immunoproteasome subunits in primary melanoma lesions exhibiting histological signs of tumour regression than in primary melanoma lesions without regression phenomena. In spontaneously regressing melanoma lesions, LMP2 and LMP7 expression was significantly associated with the presence of tumour-infiltrating lymphocytes. Our results are compatible with the possibility that the expression of the immunoproteasome subunits LMP2 and LMP7 rather than their downregulation in melanoma cells is associated with the presence of a successful anti-melanoma immune response.