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[Cancer Research 61, 6219-6226, August 15, 2001]
© 2001 American Association for Cancer Research

Immunology

Epstein-Barr Virus-specific Cytotoxic T Lymphocyte Responses in the Blood and Tumor Site of Hodgkin’s Disease Patients

Implications for a T-cell-based Therapy1

Ann L. N. Chapman, Alan B. Rickinson, Wendy A. Thomas, Ruth F. Jarrett, John Crocker and Steven P. Lee2

CRC Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, United Kingdom [A. L. N. C., A. B. R., W. A. T., S. P. L.]; Leukaemia Research Fund Virus Centre, Department of Veterinary Pathology, Veterinary School, Bearsden Road, Glasgow G61 1QH, United Kingdom [R. F. J.]; and Department of Cellular Pathology, Birmingham Heartlands Hospital, Birmingham B9 5SS, United Kingdom [J. C.]

Approximately 40% of Hodgkin’s disease (HD) cases carry EBV in the malignant Hodgkin-Reed Sternberg (H-RS) cells, with expression of viral latent membrane proteins (LMPs) 1 and 2. These viral proteins are targets for CTLs in healthy EBV carriers, and their expression in EBV-associated HD raises the possibility of targeting them for a CTL-based immunotherapy. Here we characterize the CTL response to EBV latent antigens in both the blood and tumor-infiltrating lymphocytes of HD patients using two approaches: (a) in vitro reactivation of CTLs by stimulation with the autologous EBV-transformed lymphoblastoid cell line; and (b) an enzyme-linked immunospot assay to quantify frequencies of CTLs specific for known LMP1/2 epitopes. We detected EBV-specific CTLs in blood and biopsy samples from both EBV-negative and EBV-positive HD patients. However, as in healthy EBV carriers, LMP-specific CTL precursors occurred only at low frequency in the blood of HD patients, and with the exception of one EBV-negative HD case, were undetectable in the tumor. These data give rise to two considerations: (a) they may explain why EBV-positive tumor cells persist in the presence of an existing EBV-specific immune response; and (b) they provide a rationale for selectively boosting/eliciting LMP-specific CTL responses as a therapy for EBV-positive HD.




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Copyright © 2001 by the American Association for Cancer Research.