HLA associations with nasopharyngeal carcinoma: Implications in pathogenesis and immunotherarpy

Abstract

NPC is a human epithelial tumor with a high incidence in Southern Chinese population, with contributions from HLA, EBV and environmental factors to its aetiology. The mechanisms of HLA associations are unknown. It has been hypothesized that there might be NPC disease genes located within the HLA region or it is due to the inappropriate presentation of EBV antigens by HLA molecules. We report here a population-based SNP map across the HLA region, which provided a framework to map the likely disease loci of NPC. Our disease association analysis using SNPs has brought some insights into the NPC pathogenesis by pointing out that NPC disease mutations are recessive and by refining regions needs further investigations. Apart from this, this study suggests that the molecular mechanisms underlying the HLA association with NPC are not always indirect effects due to linkage, but can also be direct effects of HLA restriction. The tetramer-assisted characterization of A1101/B4601/B5801/B2704 restricted EBV-specific T cell responses in healthy virus carriers may provide some insights into the mechanisms of HLA associations with NPC as well as assist in the development of anti-cancer vaccine.