Different altered HLA class I tumor phenotypes are produced because of immune selection (Garrido and Algarra 2001; Seliger et al. 2002). Total or selective losses of HLA class I antigens have been reported in different human tumor samples. The loss of an MHC antigen associated with H-2Kk class I molecule was first described in 1976 in a mouse lymphoma, and the detection of HLA losses in human tumors followed in 1977 (Garrido et al. 1976). In subsequent years, an increasing proportion of tumors were found to have these alterations supporting the theory that altered HLA expression phenotypes represent a major mechanism of tumor escape from T cell recognition.
We have classified all known HLA-altered phenotypes in seven groups: (i) phenotype I, HLA class I total loss (a) or downregulation (b); (ii) phenotype II, haplotype loss; (iii) phenotype III, locus loss; (iv) phenotype IV, allelic losses; (v) phenotype V, compound phenotype; (vi) phenotype VI, unresponsiveness to IFN-y; and (vii) phenotype VII, downregulation of classical HLA-A, -B, and -C molecules and appearance of non-classical HLA-E molecules (Figure 2) (Garrido et al. 1997; Aptsiauri et al. 2007).
All of these phenotypes can be found in various types of tumor, regardless of the tissue origin or of the carcinogen inducing the tumor. Differences are observed in the distribution of the phenotypes and in the combination of molecular mechanisms leading to each phenotype. An example of such distribution in various types of solid tumors and melanoma cell lines (ESTDAB project, http://www.ebi.ac.uk/ipd/estdab/) (Pawelec and Marsh 2006) is presented in Table 1.
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