The HLA crossroad in tumor immunology

Abstract

ABSTRACT:It is generally accepted that human and experimental tumor cells can lose major histocompatibility complex (MHC) class I molecules. These human leukocyte antigen (HLA) losses are detected when the primary tumor breaks the basal membrane, invades the surrounding tissues, and starts to metastasize. These altered HLA class I phenotypes probably constitute the major tumor escape mechanism facing anti-tumor T-cell mediated responses. Thus, it is important to characterize these phenotypes in clinical tumor samples, analyze the mechanism(s) responsible for them, and counsel patients before and during peptide anti-cancer immunotherapy. The present paper summarizes the most relevant altered HLA class I phenotypes found in human tumor samples, indicates their frequency, and outlines the mechanisms implicated. This review also points out that the natural killer (NK) escape mechanism of HLA class I deficient cancer cells is yet to be defined. Knowledge accumulated to date reveals that HLA class I molecules are an important crossroad in tumor immunology. Human Immunology 61, 65-73 (2000).

Dendritic cell density and activation status in human breast cancer – CD1a, CMRF-44, CMRF-56 and CD-83 expression

“…It has been proposed that CD1a acts as a lipid/carbohydrate carrying glycoprotein, similar in function to major histocompatability complex (MHC) molecules for peptides, with antigen presentation functions (Hillenbrand, 1994, Hillenbrand et al, 1999Coventry, 1999). Interestingly, classical MHC molecules are frequently completely or partially lost from tumour cells with transition from in-situ to invasive growth (Garrido et al, 1993;Algarra et al, 2000). CD1a appears to be internalized and/or downregulated as the DC matures and acquires the ability to present antigen more efficiently.…”

Downregulation of major histocompatibility complex antigens in invading glioma cells: stealth invasion of the brain

“…The idea that decreased MHC expression protects tumor cells from immune surveillance is not new. 31,[55][56][57][58] In order to be recognized by cytotoxic T cells, tumor antigens a Genes were selected based on the following criteria: (i) they were up-or downregulated beyond our cutoff threshold of Z2-fold. The fold changes are shown and were calculated as in 'Materials and methods'; (ii) they were previously associated with glioma cell migration or invasion and identified by Affymetrix microarray analysis; or (iii) they were linked to glioma cell migration or invasion by studies of gene or protein expression.…”

Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population

“…TAP is essential for MHC class Irestricted presentation of antigen, as demonstrated by absent or low expression of MHC class I molecules in TAPdeficient mice and cell lines (Spies and DeMars 1991). Tumor cell lines frequently show impaired TAP expression and/or function, underlining the key role of TAP in immune surveillance and prevention of tumor growth mediated by MHC class I proteins (Algarra et al 2000). Chen et al (1996) have described a case of human lung tumor with impaired TAP function due to a mutation in the Walker B region of TAP1, and a number of investigators have examined potential associations of TAP1 and TAP2 genotypes with altered susceptibilities to MHC-associated diseases.…”