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CD4 and CD8 T cell responses to tumour-associated Epstein–Barr virus antigens in nasopharyngeal carcinoma patients

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Abstract

Nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV)-associated tumour common in Southern Chinese populations, is a potentially important target for T cell-based immunotherapy. The tumour cells are HLA class I- and II-positive and express a limited subset of EBV latent proteins, namely the nuclear antigen EBNA1 and the latent membrane proteins LMP2 and (in some cases) LMP1. To ask whether the tumour develops in the presence of a potentially protective host response or in its absence, we set out to determine the prevailing levels of CD4+ and CD8+ T cell memory to these proteins in NPC patients at tumour diagnosis. We first screened healthy Chinese donors against Chinese strain EBNA1, LMP1 and LMP2 sequences in Elispot assays of interferon-γ release and identified the immunodominant CD4+ and CD8+ epitope peptides presented by common Chinese HLA alleles. Then, comparing 60 patients with >70 healthy controls on peptide epitope mini-panels, we found that T cell memory to CD4 epitopes in all three proteins was unimpaired in the blood of patients at diagnosis. In most cases NPC patients also showed detectable responses to CD8 epitopes relevant to their HLA type, the one consistent exception being the absence in patients of a B*4001-restricted response to LMP2. We infer that NPC arises in patients whose prevailing levels of T cell memory to tumour-associated EBV proteins is largely intact; the therapeutic goal must therefore be to re-direct the existing memory repertoire more effectively against antigen-expressing tumour cells.

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Acknowledgments

This work was supported by Cancer Research UK, by the Hong Kong Cancer Fund and by the Royal Society, London. We thank Dr. Stuart Collins (CR-UK Clinical Trials Unit, University of Birmingham) for statistical advice.

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Authors and Affiliations

  1. Sir Y. K. Pao Centre for Cancer, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong, China

    Xiaorong Lin, Edwin P. Hui, Xue Qun & Anthony T. C. Chan

  2. Cancer Research UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham, B15 2TT, UK

    Nancy H. Gudgeon, Hui Jia, Graham S. Taylor & Alan B. Rickinson

  3. Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China

    Edwin P. Hui & Anthony T. C. Chan

  4. Department of Transplant Immunology, Oxford Transplant Centre, University of Oxford, Churchill Hospital, Oxford, UK

    Martin C. N. M. Barnardo

  5. Hong Kong Red Cross Blood Transfusion Service, Kowloon, Hong Kong, China

    C. Kit Lin

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  1. Xiaorong Lin
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Correspondence to Alan B. Rickinson.

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Lin, X., Gudgeon, N.H., Hui, E.P. et al. CD4 and CD8 T cell responses to tumour-associated Epstein–Barr virus antigens in nasopharyngeal carcinoma patients. Cancer Immunol Immunother 57, 963–975 (2008). https://doi.org/10.1007/s00262-007-0427-8

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