Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
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.
Li
Jiang
J
State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Zeng
Xue-hui
XH
Mo
Hao-yuan
HY
Rolén
Ulrika
U
Gao
Yan-fang
YF
Zhang
Xiao-shi
XS
Chen
Qiu-yan
QY
Zhang
Li
L
Zeng
Mu-sheng
MS
Li
Man-zhi
MZ
Huang
Wen-lin
WL
Wang
Xiao-ning
XN
Zeng
Yi-xin
YX
Masucci
Maria G
MG
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
D000914:Antibodies, Viral; D016207:Cytokines