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...

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Autores principales: Jiang Li, Xue-hui Zeng, Hao-yuan Mo, Ulrika Rolén, Yan-fang Gao, Xiao-shi Zhang, Qiu-yan Chen, Li Zhang, Mu-sheng Zeng, Man-zhi Li, Wen-lin Huang, Xiao-ning Wang, Yi-xin Zeng, Maria G Masucci
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Publicado: Public Library of Science (PLoS) 2007
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spelling oai:doaj.org-article:9bf255423df54bef952ea29681975c602021-11-25T06:10:33ZFunctional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.1932-620310.1371/journal.pone.0001122https://doaj.org/article/9bf255423df54bef952ea29681975c602007-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0001122https://doaj.org/toc/1932-6203Nasopharyngeal 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.Jiang LiXue-hui ZengHao-yuan MoUlrika RolénYan-fang GaoXiao-shi ZhangQiu-yan ChenLi ZhangMu-sheng ZengMan-zhi LiWen-lin HuangXiao-ning WangYi-xin ZengMaria G MasucciPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 2, Iss 11, p e1122 (2007)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jiang Li
Xue-hui Zeng
Hao-yuan Mo
Ulrika Rolén
Yan-fang Gao
Xiao-shi Zhang
Qiu-yan Chen
Li Zhang
Mu-sheng Zeng
Man-zhi Li
Wen-lin Huang
Xiao-ning Wang
Yi-xin Zeng
Maria G Masucci
Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
description 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.
format article
author Jiang Li
Xue-hui Zeng
Hao-yuan Mo
Ulrika Rolén
Yan-fang Gao
Xiao-shi Zhang
Qiu-yan Chen
Li Zhang
Mu-sheng Zeng
Man-zhi Li
Wen-lin Huang
Xiao-ning Wang
Yi-xin Zeng
Maria G Masucci
author_facet Jiang Li
Xue-hui Zeng
Hao-yuan Mo
Ulrika Rolén
Yan-fang Gao
Xiao-shi Zhang
Qiu-yan Chen
Li Zhang
Mu-sheng Zeng
Man-zhi Li
Wen-lin Huang
Xiao-ning Wang
Yi-xin Zeng
Maria G Masucci
author_sort Jiang Li
title Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
title_short Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
title_full Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
title_fullStr Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
title_full_unstemmed Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
title_sort functional inactivation of ebv-specific t-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
publisher Public Library of Science (PLoS)
publishDate 2007
url https://doaj.org/article/9bf255423df54bef952ea29681975c60
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