AN IMMUNOHISTOCHEMICAL STUDY OF ALTERED IMMUNOMODULATORY MOLECULE EXPRESSION IN HEAD AND NECK SQUAMOUS-CELL CARCINOMA

For the presentation of peptide antigens to cytotoxic CD8(+) T lymphoc ytes of the immune system, the expression of human leukocyte antigen ( HLA) class I molecules on the cell surface is necessary. There is incr easing evidence that surface HLA class I antigen expression is altered in a variety of human tumours by either loss or down-regulation of th ese molecules, which may be a Strategy for evasion of immunosurveillan ce by malignant cells. This study has examined the expression of HLA c lass I molecules in head and neck squamous cell carcinoma (HNSCC) spec imens by immunohistochemistry, using a wide panel of antibodies direct ed against allele-specific as well as monomorphic determinants of thes e molecules. The expression of TAP proteins, HLA-DR and the co-stimula tory molecule ICAM-1 were also studied. In addition, the expression of the tumour-associated antigens (TAA) p53 and MAGE genes was determine d. Aberrant allelic expression of HLA class I antigens was detected in 17 out of 34 (50%) of the specimens stained, whereas HLA class I expr ession determined by W6/32 staining was found to be heterogeneous in o nly 2 out of 34 (6%) cases. Decreased expression of ICAM-1 was observe d in 12 out of 34 (35%) tumour specimens and de novo expression of HLA -DR (HLA class II) by carcinoma cells in 13 out of 34 (38%) cases. Abe rrant expression of HLA class I antigens was frequently observed in ca ses in which MAGE genes and p53 overexpression were detected. The alte red expression of these immunomodulatory molecules in HNSCC may affect prognosis and has important implications for peptide-based immunother apy strategies for these patients.