Down-regulation of locus-specific human lymphocyte antigen class I expression in epstein-barr virus-associated gastric cancer : Implication for viral-induced immune evasion

• Published in: Cancer 2006-04, Vol.106 (8), p.1685-1693
• Main Authors: DUTTA, Nirmal, GUPTA, Arnab, NATH GUHA MAZUMDER, Debendra, BANERJEE, Subrata
• Format: Article
• Language: English
• Subjects: Antigens, Surface - biosynthesis; Biological and medical sciences; Down-Regulation; Epstein-Barr Virus Infections - immunology; Flow Cytometry; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Herpesvirus 4, Human - immunology; Herpesvirus 4, Human - isolation & purification; Histocompatibility Antigens Class I - biosynthesis; Histocompatibility Antigens Class I - genetics; Humans; In Situ Hybridization; Medical sciences; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms - genetics; Stomach Neoplasms - immunology; Stomach Neoplasms - virology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21784

To understand whether the association between Epstein-Barr Virus (EBV) and gastric cancer (GC) has any role in loss of surface expression of human lymphocyte antigen (HLA) class I, the authors analyzed locus-specific transcriptional expression of HLA-A, HLA-B, HLA-C, and HLA-E along with other HLA-associated molecules (beta2-microglobulin [beta2M], cellular latent membrane protein [LMP], and transporter associated with antigen presentation [TAP]) in EBV-associated, primary GC (EBVaGC) and EBV-negative GC (EBVnGC) tissues. Approximately 20 EBVaGC tissues and 40 EBVnGC tissues and their corresponding normal tissues were used in the study. The presence of EBV in GC was established by EBV-encoded small RNA in situ hybridization analysis and BamHI W polymerase chain reaction (PCR) analysis. Transcriptional expression of viral LMP2A and several HLA class I genes were analyzed by reverse transcriptase (RT)-PCR. Surface expression levels of HLA class I proteins in cancer samples along with their normal counterparts also were quantified by flow cytometry. The RT-PCR data suggested selective down-regulation of the HLA-A/HLA-B locus along with over-expression of HLA-E transcripts in EBVaGC (P < .05). This was confirmed further by the flow-cytometric studies using antibodies to HLA-ABC and HLA-E. Among the accessory molecules, LMP7 transcript was down-regulated in a number of EBVaGC tissues compared with EBVnGC. The current results suggested that the establishment of EBV latent infection in gastric tissues allows malignant cells to avoid the immune surveillance of both cytotoxic T-lymphocytes and natural killer cells by regulating the differential expression of HLA class I molecules.