title: Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein-Barr virus associated nasopharyngeal carcinoma.
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.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Fogg
authors.forename: John R
authors.initials: JR
authors.lastname: Murphy
authors.forename: Jochen
authors.initials: J
authors.lastname: Lorch
authors.forename: Marshall
authors.initials: M
authors.lastname: Posner
authors.forename: Fred
authors.initials: F
authors.lastname: Wang
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002277:Carcinoma; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; C417029:EBV-encoded nuclear antigen 1