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

Abstract

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-g inducible proteasome subunits and of the peptide transporterTAP 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, andTAP1down-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-g. 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.

Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+ Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

“…Similar to other HNSCC, having high expression of HLA class I was recently shown to correlate to better outcome in HPV − tonsillar and base of tongue SCC, while surprisingly having absent/weak expression correlated to a better prognosis in HPV + tonsillar and base of tongue SCC (20,(31)(32). Here, the corresponding correlations were not found.…”

CD4+ T helper responses in squamous cell carcinoma of the head and neck

“…18 Using immunohistochemistry, Meissner et al have reported that HLA class I antigens were not detectable in 12% of the lesions from SCCHN. 19 It is generally accepted that IFN-γ transcriptionally modulates the expression of HLA class I antigens and of antigen processing machinery components, including the proteasome subunits LMP2, LMP7, and LMP10. 20 However, when Gun-1 cells were treated with IFN-γ and examined for HLA-A2 expression by flow cytometry, we failed to up-regulate HLA-A2 expression on these cells.…”

The link between MHC class I abnormalities of tumors, oncogenes, tumor suppressor genes, and transcription factors

“…Moreover, down-regulation of MHC class I surface expression correlates in primary lesions with thickness, advanced disease stage, as well as with shorter time to progression rates. Correlations between MHC class I APM abnormalities and the clinical outcome of patients have not only been described for melanoma, but also for other malignancies including RCC, prostate, cervical, ovarian, and head and neck squamous cell carcinoma (Atkins et al, 2004;Ferris et al, 2006;Kageshita et al, 1999;Mehta et al, 2008;Meissner et al, 2005;Vitale et al, 1998). In prostate cancer, down-regulation of MHC class I molecules did correlate with higher progression rates and early tumor recurrence, which can be further accompanied with reduced or even loss of TAP1 and ERAP1 expression levels (Norell et al, 2006;Seliger et al, 2010).…”