Hla Class I Antigens in Human Tumors

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This chapter focuses on the abnormal major histocompatibility complex (MHC) expression detected in human tumors as well as on the biological role that these alterations may have in tumor development. The potential therapeutic implications of these discoveries are discussed in the chapter. MHC constitutes a set of genes that synthesize products specializing in the processing and presentation of endogenous and exogenous antigens to the immune system. Four major categories of genes are involved in this genetically controlled process: class I, class II, proteasome, and transported genes. A major characteristic of these genes is their very high degree of polymorphism. Polymorphism provides an enormous diversity of antigenic peptides that can potentially be presented, conferring to a given species the possibility of generating an immune response to a particular antigen, even though a given individual might not have the set of alleles required to do so. Human leukocyte antigen (HLA) class I molecules are ternary complexes formed by a heavy chain, a light chain of P2-microglobulin (Pam), and a peptide. Significant changes in HLA expression in tumor cells are assessed by determining the proportion of neoplastic cells that exhibit differences in immunohistochemical labeling in comparison with normal tissues from the same specimen. The role of MHC in T and NK cell recognition is discussed in the chapter. Progress in HLA class I gene transfer in cancer patients requires the precise identification of the HLA antigen losses and mechanisms responsible for HLA downregulation. Routine methods for the straightforward and accurate identification of HLA antigen losses are not yet available. The XII HLA Histocompatibility Workshop has created a new component designated “HLA and Cancer” that coordinates data from different laboratories to help achieve these aims.

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