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PMID: 17987110 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.

PloS one ·Vol. 2 ·No. 11 ·2007-11-07 ·Pages e1122

Li J, Zeng XH, Mo HY, Rolén U, Gao YF, Zhang XS, Chen QY, Zhang L, Zeng MS, Li MZ, Huang WL, Wang XN, Zeng YX, Masucci MG

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.

MeSH Terms
Antibodies, Viral/blood Carrier State Cytokines/blood Herpesvirus 4, Human/immunology,isolation & purification Humans Immunophenotyping Immunotherapy In Situ Hybridization Lymphocyte Activation Nasopharyngeal Neoplasms/immunology,therapy,virology T-Lymphocytes/immunology Viral Load
Chemicals
Antibodies, Viral Cytokines
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Li Jiang
State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Zeng Xue-hui
Mo Hao-yuan
Rolén Ulrika
Gao Yan-fang
Zhang Xiao-shi
Chen Qiu-yan
Zhang Li
Zeng Mu-sheng
Li Man-zhi
Huang Wen-lin
Wang Xiao-ning
Zeng Yi-xin
Masucci Maria G
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0001122
Published
2007-11-07
Epub
2007-00-07
Pages
e1122
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2048575
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0001122 PMC Full Text View journal details
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