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HLA Class I Expression in Human Cancer

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MHC Class I Antigens In Malignant Cells

Part of the book series: SpringerBriefs in Cancer Research ((BRIEFSCANCER,volume 6))

Abstract

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 first 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 first, 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 findings did not attract much attention and were not considered to be significant. Later on, with the appearance of more specific monoclonal antibodies (anti-locus-A, -B and anti-allele-specific 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-specific 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.

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  1. Servicio de Análisis Clínicos, Hosp. Universitario Virgen de las Nieves, Granada, Spain

    Natalia Aptsiauri & Angel Miguel Garcia-Lora

  2. Departamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada, Granada, Spain

    Teresa Cabrera

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  1. Natalia Aptsiauri
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Aptsiauri, N., Garcia-Lora, A.M., Cabrera, T. (2013). HLA Class I Expression in Human Cancer. In: MHC Class I Antigens In Malignant Cells. SpringerBriefs in Cancer Research, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6543-0_2

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