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Down-Regulation of HLA Class I Antigen Processing Molecules: An Immune Escape Mechanism of Renal Cell Carcinoma?

2004; Lippincott Williams & Wilkins; Volume: 171; Issue: 2 Linguagem: Inglês

10.1097/01.ju.0000094807.95420.fe

1527-3792

Derek Atkins, Soldano Ferrone, Gerd E. Schmahl, Stefan Störkel, Barbara Seliger,

Bladder and Urothelial Cancer Treatments

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Feb 2004Down-Regulation of HLA Class I Antigen Processing Molecules: An Immune Escape Mechanism of Renal Cell Carcinoma? DEREK ATKINS, SOLDANO FERRONE, GERD E. SCHMAHL, STEFAN STÖRKEL, and BARBARA SELIGER DEREK ATKINSDEREK ATKINS , SOLDANO FERRONESOLDANO FERRONE , GERD E. SCHMAHLGERD E. SCHMAHL , STEFAN STÖRKELSTEFAN STÖRKEL , and BARBARA SELIGERBARBARA SELIGER View All Author Informationhttps://doi.org/10.1097/01.ju.0000094807.95420.feAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Proper HLA class I antigen processing and presentation is a prerequisite for the recognition of tumor cells by cytotoxic T lymphocytes. To date there exist only limited information on the expression of components of the HLA class I associated antigen processing machinery (APM) in surgically removed benign renal cell adenoma, and primary and metastatic renal cell carcinoma (RCC). Materials and Methods: A total of 133 primary RCCs of different subtypes, 10 renal cell adenoma biopsies, 32 matched metastases of different localization and autologous normal kidney epithelium were immunohistochemically analyzed for the expression of HLA class I antigens, low molecular weight protein (LMP)2 and LMP7, the transporter associated with antigen processing subunit (TAP1) and β2-microglobulin (β2-m). Results: Normal kidney tissue showed strong cytoplasmic staining intensity for LMP2, LMP7 and TAP1, whereas β2-m and HLA class I heavy chains were detected on the cell surface. A low frequency of HLA class I HC and β2-m down-regulation was found in RCC. In contrast, primary RCC and metastases showed a high frequency of a total lack of heterogeneous TAP1, LMP2 and LMP7 expression, which was often coordinately regulated. APM component deficiencies were associated with RCC subtypes but not with tumor grading and staging. Conclusions: HLA class I APM component abnormalities appear to represent an immune escape mechanism of RCC. This finding emphasizes the need to evaluate the integrity and expression of these molecules in patients with RCC, especially in those selected for treatment with T-cell based immunotherapy. References 1 : Cancer statistics, 1998. CA Cancer J Clin1998; 48: 6. Google Scholar 2 : Renal cell carcinoma: management of advanced disease. J Urol1999; 161: 381. Link, Google Scholar 3 : Therapeutic options in the management of renal cell carcinoma. Semin Oncol2002; 29: 41. Google Scholar 4 : Cytokine therapy for metastatic renal cell carcinoma. Semin Urol Oncol2001; 19: 148. 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Cancer Res1996; 56: 1756. Google Scholar From the IIIrd Department of Internal Medicine, Johannes Gutenberg-University (DA, BS), Mainz and Institute of Pathology, University Witten/Herdecke (DA, GES, SS), 42283 Wuppertal, Federal Republic of Germany, and Department of Immunology, Roswell Park Cancer Institute (SF), Buffalo, New York© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byKitamura H, Honma I, Torigoe T, Asanuma H, Sato N and Tsukamoto T (2018) Down-Regulation of HLA Class I Antigen is an Independent Prognostic Factor for Clear Cell Renal Cell CarcinomaJournal of Urology, VOL. 177, NO. 4, (1269-1272), Online publication date: 1-Apr-2007. Volume 171Issue 2February 2004Page: 885-889 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordscarcinoma, renal cellHLA antigensT-lymphocytesadenoma, adrenal corticalkidneyMetricsAuthor Information DEREK ATKINS More articles by this author SOLDANO FERRONE More articles by this author GERD E. SCHMAHL More articles by this author STEFAN STÖRKEL More articles by this author BARBARA SELIGER More articles by this author Expand All Advertisement PDF downloadLoading ...