title: Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
abstract: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignancy with high prevalence in Southern Chinese. In order to assess whether defects of EBV-specific immunity may contribute to the tumor, the phenotype and function of circulating T-cells and tumor infiltrating lymphocytes (TILs) were investigated in untreated NPC patients. Circulating naïve CD3+CD45RA+ and CD4+CD25- cells were decreased, while activated CD4+CD25+ T-cells and CD3-CD16+ NK-cells were increased in patients compared to healthy donors. The frequency of T-cells recognizing seven HLA-A2 restricted epitopes in LMP1 and LMP2 was lower in the patients and remained low after stimulation with autologous EBV-carrying cells. TILs expanded in low doses of IL-2 exhibited an increase of CD3+CD4+, CD3+CD45RO+ and CD4+CD25+ cells and 2 to 5 fold higher frequency of LMP1 and LMP2 tetramer positive cells compared to peripheral blood. EBV-specific cytotoxicity could be reactivated from the blood of most patients, whereas the TILs lacked cytotoxic activity and failed to produce IFNgamma upon specific stimulation. Thus, EBV-specific rejection responses appear to be functionally inactivated at the tumor site in NPC.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Xue-hui
authors.initials: XH
authors.lastname: Zeng
authors.forename: Hao-yuan
authors.initials: HY
authors.lastname: Mo
authors.forename: Ulrika
authors.initials: U
authors.lastname: Rolén
authors.forename: Yan-fang
authors.initials: YF
authors.lastname: Gao
authors.forename: Xiao-shi
authors.initials: XS
authors.lastname: Zhang
authors.forename: Qiu-yan
authors.initials: QY
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Mu-sheng
authors.initials: MS
authors.lastname: Zeng
authors.forename: Man-zhi
authors.initials: MZ
authors.lastname: Li
authors.forename: Wen-lin
authors.initials: WL
authors.lastname: Huang
authors.forename: Xiao-ning
authors.initials: XN
authors.lastname: Wang
authors.forename: Yi-xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Maria G
authors.initials: MG
authors.lastname: Masucci
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D002353:Carrier State; D016207:Cytokines / Q000097:blood; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D017403:In Situ Hybridization; D008213:Lymphocyte Activation; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines