Undifferentiated nasopharyngeal carcinoma from a nonendemic area: Protective role of HLA allele products presenting conserved EBV epitopes

Elisa Pasini, Laura Caggiari, Luigino Dal Maso, Debora Martorelli, Massimo Guidoboni, Emanuela Vaccher, Luigi Barzan, Giovanni Franchin, Annunziata Gloghini, Valli De Re, Nicoletta Sacchi, Diego Serraino, Antonino Carbone, Antonio Rosato, Riccardo Dolcetti

Research output: Contribution to journalArticlepeer-review

Abstract

The role of genetic factors involved in the development of undifferentiated nasopharyngeal carcinoma (UNPC) in nonendemic areas has been poorly investigated. High-resolution human leukocyte antigen (HLA) class I genotyping carried out in 82 Italian UNPC patients and 286 bone marrow donors born in the same province showed that A*0201, B*1801, and B*3501, known to effi-ciently present Epstein-Barr virus (EBV)-derived epitopes, were significantly under-represented in UNPC patients. Moreover, the A*0201/B*1801 haplotype was significantly less frequent in UNPC cases, with a 90% reduced risk (odds ratio [OR] 0.1, 95% confi-dence interval [CI] = 0.0-0.5) to develop UNPC, suggesting an additive effect. Notably, all 5 BARF1 epitopes and 7 of the 8 LMP-2 epitopes known to bind A*0201 showed a fully conserved sequence in all the 31 Italian EBV isolates investigated. The 4 amino acid changes affecting the 436-447 LMP-2 epitope do not reduce, but rather increase in two cases, the predicted ability of "variant" epitopes to bind the HLA-A*0201 allele, as shown by immunoinformatic analysis. Moreover, a significantly increased risk for UNPC was associated with A*2601 (OR 2.4, 95% CI = 1.1-4.9) and B*4101 (OR 9.2, 95% CI = 2.5-34.3). These findings indicate that Italian UNPC patients have a distinct HLA-A and -B genotypic profile and suggest that the decreased risk for UNPC conferred by definite HLA class I molecules is probably related to their ability to efficiently present LMP-2 and BARF1 epitopes that are highly conserved in EBV isolates from this geographic region. These results have practical implications for the immunotherapy of UNPC.

Original languageEnglish
Pages (from-to)1358-1364
Number of pages7
JournalInternational Journal of Cancer
Volume125
Issue number6
DOIs
Publication statusPublished - Sep 15 2009

Keywords

  • BARF1
  • Epstein-Barr virus
  • HLA
  • LMP2
  • Nasopharyngeal carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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