ALTERED MHC CLASS-I ANTIGENS IN TUMORS

MHC class I antigens are lost or downregulated in invasive tumors comp ared with autologous normal tissues. This is observed in most of the n ewly induced experimental tumors analyzed if they are cloned before pa ssaging in vivo. Similarly, this is observed in 40%-90% of human tumor s using the available panel of anti-HLA class I monoclonal antibodies. In both systems the tumor populations are heterogeneous for H-2/HLA e xpression and composed of clones that express different amounts of MHC class I antigens. This heterogeneity may have a profound influence on tumor behavior, considering the role that MHC antigens play in T and natural killer cell-mediated responses. It is possible that the tumor escape mechanisms from T and natural killer cells select variants that express a particular MHC class I altered phenotype. We review the MHC changes detected in different experimental as well as human tumors an d demonstrate the relevance of these altered H-2/HLA tumor phenotypes for implementing immunotherapeutic strategies based on T or natural ki ller cell-mediated responses.