Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein-Barr virus associated nasopharyngeal carcinoma

Mark Fogg, John R. Murphy, Jochen Lorch, Marshall Posner, Fred Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Epstein-Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients.

Original languageEnglish (US)
Pages (from-to)107-113
Number of pages7
JournalVirology
Volume441
Issue number2
DOIs
StatePublished - Jul 5 2013

Funding

This work was supported by Grants from the Dana Farber Cancer Institute Friends of Head and Neck Cancer Research and the National Institutes of Health ( CA68051 , CA132279 ). We thank the Head and Neck Clinical Research Team at the DFCI for managing clinical sample collection and all of the NPC patients and healthy donors who so generously contributed blood for these studies. Appendix A

Keywords

  • CD8+ T cells
  • Epstein-Barr virus
  • Nasopharyngeal carcinoma
  • Ontak
  • T regulatory cells

ASJC Scopus subject areas

  • Virology

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