Human leukocyte antigen class I allelic and haplotype loss in squamous cell carcinoma of the head and neck: Clinical and immunogenetic consequences

The expression of human leukocyte antigen (HLA) class I molecules on the ce ll surface is necessary for the presentation of peptide antigens to cytotox ic CD8+ T lymphocytes of the immune system. Down-regulation of HLA class I gene expression has been implicated in tumorigenesis, including squamous ce ll carcinoma of the head and neck (SCCHN), Loss of MHC class I antigens may be one mechanism by which tumor cells escape immune detection, We performe d prospective immunostaining of 26 primary SCCHN tumors and samples of norm al mucosa harvested several centimeters away from the primary tumor, using a large panel of antibodies directed against allele-specific as well as mon omorphic determinants of HLA class I molecules. Loss of expression of HLA c lass I proteins in the tumor was found in 50% (13 of 26) of primary tumors and was highly correlated with HLA loss in the corresponding normal mucosa (P < 0.0001), Further analysis demonstrated that the loss of HLA class I ex pression in the tumor was significantly associated with regional lymph node metastases (nodal stage; P = 0.0388), and that the number of HLA class I a lleles lost in the normal mucosa was associated with subsequent development of a new primary aerodigestive tract cancer (P = 0.042), A patient with tw o metachronous cancers available for analysis had no evidence of HLA loss i n the first tumor, demonstrated allelic loss in the second cancer, and subs equently died of disease. These results suggest that the loss of expression of HLA class I alleles may have prognostic implications.