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Defects in the Human Leukocyte Antigen Class I Antigen Processing Machinery in Head and Neck Squamous Cell Carcinoma: Association with Clinical Outcome

Authors' Affiliations: Departments of ¹ Internal Medicine and ² Oral and Maxillofacial Surgery, Johannes Gutenberg-University, Mainz; ³ Department of Dermatology, Johann Wolfgang Goethe-University, Frankfurt; ⁴ Institute of Medical Immunology, Martin-Luther University, Halle, Germany; ⁵ Division of Biostatistics and ⁶ Departments of Pathology and Otolaryngology, School of Medicine and Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; and ⁷ Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York

Requests for reprints: Barbara Seliger, Institute of Medical Immunology, Martin-Luther University, Magdeburger Str. 2, 06112 Halle, Germany. Phone: 49-345-557-4054; Fax: 49-345-557-4055; E-mail: Barbara.Seliger{at}medizin.uni-halle.de.

Purpose: Human leukocyte antigen (HLA) class I antigen defects, which are frequently present in head and neck squamous cell carcinoma (HNSCC) cells may provide the tumor with an escape mechanism from immune surveillance. Scanty information is available about mechanisms underlying HLA class I antigen defects in both lesions and cell lines from HNSCC. In this study, we investigate the role of antigen processing machinery (APM) component abnormalities in the generation of deficient HLA class I surface expression of HNSCC cells.

Experimental Design: Using immunohistochemistry, Western blot, and RT-PCR analyses we correlated the expression of the IFN- inducible proteasome subunits and of the peptide transporter TAP with that of HLA class I antigens in biopsies and cell lines from primary, recurrent, and metastatic HNSCC. Furthermore, APM component and HLA class I antigen expression in surgically removed lesions were correlated with the course of the disease in order to assess the clinical significance of deficient expression of these molecules.

Results: A high frequency of LMP2, LMP7, and TAP1 down-regulation or loss was found in tumor lesions and cell lines obtained from HNSCC cancer patients. These defects could be corrected by incubating cells with IFN-. Furthermore, LMP2, LMP7, TAP1, TAP2, and HLA class I antigen expression rates in primary HNSCC lesions were found to predict overall survival. Lastly, the level of LMP7 expression was significantly associated with disease recurrence at 2 years.

Conclusions: Our results suggest that the analysis of APM component expression in HNSCC lesions can provide useful prognostic information in patients with HNSCC.

Key Words: head and neck cancer • MHC class I • antigen processing • prognostic marker

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