An immunohistochemical study of altered immunomodulatory molecule expression in head and neck squamous cell carcinoma

Abstract

Summary For the presentation of peptide antigens to cytotoxic CD8+ T lymphocytes of the immune system, the expression of human leukocyte antigen (HLA) class I molecules on the cell surface is necessary. There is increasing evidence that surface HLA class antigen expression is altered in a variety of human tumours by either loss or down-regulation of these molecules, which may be a strategy for evasion of immunosurveillance by malignant cells. This study has examined the expression of HLA class molecules in head and neck squamous cell carcinoma (HNSCC) specimens by immunohistochemistry, using a wide panel of antibodies directed against allele-specific as well as monomorphic determinants of these molecules. The expression of TAP proteins, HLA-DR and the co-stimulatory molecule ICAM-1 were also studied. In addition, the expression of the tumour-associated antigens (TAA) p53 and MAGE genes was determined. Aberrant allelic expression of HLA class antigens was detected in 17 out of 34 (50%) of the specimens stained, whereas HLA class I expression determined by W6/32 staining was found to be heterogeneous in only 2 out of 34 (6%) cases. Decreased expression of ICAM-1 was observed in 12 out of 34 (35%) tumour specimens and de novo expression of HLA-DR (HLA class 11) by carcinoma cells in 13 out of 34 (38%) cases. Aberrant expression of HLA class I antigens was frequently observed in cases in which MAGE genes and p53 overexpression were detected. The altered expression of these immunomodulatory molecules in HNSCC may affect prognosis and has important implications for peptide-based immunotherapy strategies for these patients.

HLA class I antigen and transporter associated with antigen processing downregulation in metastatic lesions of head and neck squamous cell carcinoma as a marker of poor prognosis

“…Immunohistochemical staining of HNSCC lesions has yielded conflicting data on TAP expression. Vora et al (17) reported that TAP1 and TAP2 were downregulated in only 2 (9%) and 0 (0%) of 34 primary HNSCC lesions tested, respectively. Feenstra et al (28) reported that TAP1 and TAP2 were downregulated in 28 Table III.…”

“…Immunohistochemical staining of frozen and/or formalin-fixed, paraffin-embedded HNSCC primary lesions has detected HLA class I antigen loss and downregulation with a frequency ranging from 6 to 81% (14)(15)(16)(17)(18)(19)(20)(21) information is available on the role of TAP1, TAP2 and tapasin defects in the generation of the abnormal HLA class I antigen phenotypes identified in HNSCC lesions. The lack of this information has a negative impact on the design of strategies to correct HLA class I antigen defects in HNSCC lesions.…”

High frequency of HLA-B44 allelic losses in human solid tumors

“…HLA class I alleles differ in their requirements for antigen processing components; for example, tumors frequently exhibit alterations in the levels of TAP1-2, LMP2, LMP7, or tapasin expression [22][23][24]. Some alleles, such as HLA-A2, maintain their expression despite low levels of TAP1-2 or tapasin [25,26], whereas others, such as HLA-B44, have strict requirements for certain antigen processing components [27][28][29].…”

Downregulation of HLA Class I molecules in the tumour is associated with a poor prognosis in patients with oesophageal squamous cell carcinoma

“…Although immunohistochemical analyses of HLA class I expression in several malignancies have previously been performed, there was a discrepancy in the frequencies of downregulated HLA class I molecules (Mattijssen et al, 1991;Möller et al, 1991;Passlick et al, 1996;Vora et al, 1997;Ramnath et al, 2006;Kikuchi et al, 2007;Mehta et al, 2008;Speetjens et al, 2008). This discrepancy might be due to a difficulty in evaluating immunostaining by anti-MHC class I monoclonal antibodies (mAbs), such as W6/32, HC-10, or HC-A2, as these anti-MHC class I mAbs were not appropriate for the immunostaining of formalin-fixed, paraffin-embedded tissue.…”