CTL control of EBV in nasopharyngeal carcinoma (NPC): EBV-specific CTL responses in the blood and tumors of NPC patients and the antigen-processing function of the tumor cells

J Immunol. 2000 Jul 1;165(1):573-82. doi: 10.4049/jimmunol.165.1.573.

Abstract

Undifferentiated nasopharyngeal carcinoma (NPC) is latently infected with EBV and expresses a restricted number of viral proteins. Studies in healthy virus carriers have demonstrated that at least some of these proteins can act as targets for HLA class I-restricted CTLs. Therefore we have explored the possibility of a CTL-based therapy for NPC by characterizing EBV-specific CTL responses in 10 newly diagnosed NPC cases and 21 healthy virus carriers from Southeast Asia. Using the autologous EBV-transformed lymphoblastoid cell line, virus-specific CTL were reactivated in vitro from PBMC, cloned, and screened for cytotoxicity against target cells expressing individual EBV proteins from recombinant vaccinia vectors. EBV-specific CTLs were identified in 6 of 10 patients and 14 of 21 controls and mainly targeted the EBV nuclear Ag 3 (EBNA3) family of viral latent proteins. However, in 3 of 10 patients and 11 of 21 controls, CTLs specific for the NPC-associated protein LMP2 were also detected, albeit at low frequency. EBV-specific CTLs were detected in tumor biopsy material obtained from 3 of 6 of the patients, indicating that functional CTL are present at the tumor site, but none was specific for tumor-associated viral proteins. To assess the Ag-presenting function in NPC we studied two NPC-derived cell lines (C15 and c666.1) and demonstrated that both were capable of processing and presenting endogenously synthesized protein to HLA class I-restricted CTL clones. Overall, our data provide a sound theoretical basis for therapeutic strategies that aim to boost or elicit LMP2-specific CTL responses in NPC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • Antigen-Presenting Cells / pathology
  • Cell Line, Transformed
  • Cytotoxicity, Immunologic*
  • Epitopes, T-Lymphocyte / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Lymphocyte Activation
  • Mice
  • Mice, Nude
  • Middle Aged
  • Molecular Sequence Data
  • Nasopharyngeal Neoplasms / blood
  • Nasopharyngeal Neoplasms / immunology*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology
  • Tumor Cells, Cultured
  • Tumor Virus Infections / blood
  • Tumor Virus Infections / immunology*
  • Tumor Virus Infections / pathology

Substances

  • Epitopes, T-Lymphocyte