Altered HLA Class I Expression in Malignant Cells

Loss or down-regulation of HLA class I antigens in tumor cells has been frequently observed in a variety of human malignancies and it represents an important cancer immune escape mechanism (Garrido et al. 1997a ; Marincola et al. 2000 ; Campoli et al. 2002 ; Chang et al. 2005 ; Aptsiauri et al. 2007 ). Viruses use similar mechanism to avoid recognition and elimination by the immune system (Ploegh 1998 ). The fi rst description of MHC class I loss was done in a mouse model (Gardener lymphoma) in Dr. Festenstein laboratory in 1976 (Garrido et al. 1976a , b ). The production and characterization of monoclonal antibodies against HLA molecules (Barnstable et al. 1978 ) made possible to analyze HLA expression in human cell lines and solid tumors. At fi rst, the reported percentage of HLA class I loss was low (10–30 %) (Garrido et al. 1993 ), since only monomorphic monoclonal antibodies (recognizing an epitope common to all HLA class I molecules) were available at that time. These studies were able to detect only total loss of tumor HLA class I expression and due to low incidence these fi ndings did not attract much attention and were not considered to be signifi cant. Later on, with the appearance of more specifi c monoclonal antibodies (anti-locus-A, -B and anti-allele-specifi c antibodies), which recognize polymorphic portions of these molecules, the incidence of HLA altered expression in cancer has been found to be much higher, increasing the relevance of these defects in the immune response against tumor. Using a broad panel of monoclonal antibodies on cryostat tumor tissue sections these alterations have been found in 60–90 % of tumors depending on the histological type of cancer (Blades et al. 1995 ; Cabrera et al. 1996 , 1998 , 2000 ; Koopman et al. 2000 ; Kageshita et al. 2005 ). Unfortunately, the number of available allele-specifi c monoclonal antibodies is still limited. Therefore, the true percentage of HLA class I defects, especially allelic losses, may perhaps be much higher in different types of malignancy. Thus, early studies using immunohistological analysis of different tumors showed a very low frequency of allelic loss. However, with the arrival of other techniques, such as the study of microsatellites to detect loss of heterozygosity Chapter 2 HLA Class I Expression in Human Cancer