LOSS OF ANTIGEN-PRESENTING MOLECULES (MHC CLASS-I AND TAP-1) IN LUNG-CANCER

Presentation of endogenous antigenic peptides to cytotoxic T lymphocyt es is mediated by the major histocompatibility complex (MHC) class I m olecules. For the stable assembly of MHC class I complex it is necessa ry that the antigenic peptide is transported by the MHC-encoded transp orters TAP-1 and TAP-2 into a pre-Golgi region. T-cell-mediated host-v s-tumour response might therefore depend on the presence of these mole cules on tumour cells. The presence of MHC class I antigens and TAP-1 was studied in a series of 93 resection specimens of non-small-cell lu ng carcinomas (NSCLCs) by immunohistochemical methods using antibodies against the assembled class I molecule, beta(2)-microglobulin (beta(2 )-m), heavy-chain A locus, A2 allele and TAP-1 protein. Eighty-six pat ients were included in the survival analysis. Total loss of class I mo lecule was observed in 38% of the cases and was usually accompanied by loss of beta(2)-m and of heavy chain A locus. Selective loss of A loc us was seen in 8.3% and of A2 allele in 27% of the cases. TAP-1 loss w as always combined with beta(2)-m and/or heavy chain A locus loss. No correlation was found between the expressional status of any of the ab ove molecules, including the selective A2 allelic loss and histologica l type, degree of differentiation, tumoral stage, nodal stage and surv ival. Our findings suggest that loss of antigen-presenting molecules ( including both MHC class I alleles and TAP-I) is a frequent event in l ung cancer. However, the immunophenotypic profile of MHC class I and T AP-1 seems to be unrelated in vivo to the phenotype, growth or surviva l of NSCLC.