Increased frequency of antigen-specific CD8(+) cytotoxic T lymphocytes infiltrating an Epstein-Barr virus-associated gastric carcinoma

J Clin Invest. 1999 Jul;104(2):163-71. doi: 10.1172/JCI6062.


Gastric adenocarcinomas carrying Epstein-Barr virus (EBV) are known to be accompanied by massive lymphocyte infiltration. To characterize the tumor-infiltrating lymphocytes (TILs), we isolated and cultured such cells from a surgically resected EBV-associated gastric carcinoma. They were found to be positive for CD3, CD8, T-cell receptor beta chain, and cytotoxic molecules. The isolated TILs consisted of human leukocyte antigen (HLA) class I-restricted CD8(+) cytotoxic T lymphocytes (CTLs), which killed autologous EBV-transformed cells (but not phytohemagglutinin blast cells) and recognized HLA-A24 as restriction molecules. However, the TILs did not recognize known EBV antigenic peptides presented by HLA-A24 molecules, nor HLA-A24(+) fibroblasts infected with vaccinia recombinant virus expressing each of the EBV latent proteins. EBV(+) gastric carcinomas do not express conventional target proteins of EBV-specific CTLs, and the data suggest that some cellular proteins may be involved in the strong T-cell response to EBV-associated gastric carcinoma. In addition, our data suggest that class I-restricted, antigen-specific CD8(+) CTLs are specifically expanded within EBV(+) gastric carcinoma tissue.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • HLA-A Antigens / immunology
  • HLA-A24 Antigen
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / virology
  • T-Lymphocytes, Cytotoxic / immunology*


  • HLA-A Antigens
  • HLA-A24 Antigen