Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.
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DOI：
10.1371/journal.pone.0001122
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发表时间：
2007-11-07
期刊：
影响因子：
3.7
通讯作者：
Masucci MG
中科院分区：
文献类型：
--
作者：
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
鼻咽癌（NPC）是一种与EB病毒（EBV）相关的恶性肿瘤，在中国南方地区发病率较高。为了评估 EBV 特异性免疫缺陷是否可能导致肿瘤，对未经治疗的鼻咽癌患者的循环 T 细胞和肿瘤浸润淋巴细胞 (TIL) 的表型和功能进行了研究。与健康供体相比，患者的循环初始 CD3+CD45RA+ 和 CD4+CD25− 细胞减少，而活化的 CD4+CD25+ T 细胞和 CD3−CD16+ NK 细胞增加。患者中 T 细胞识别 LMP1 和 LMP2 中 7 个 HLA-A2 限制性表位的频率较低，并且在用自体 EBV 携带细胞刺激后仍保持较低水平。与外周血相比，在低剂量IL-2中扩增的TIL表现出CD3+CD4+、CD3+CD45RO+和CD4+CD25+细胞的增加，以及LMP1和LMP2四聚体阳性细胞的频率高2至5倍。 EBV特异性细胞毒性可以从大多数患者的血液中重新激活，而TIL缺乏细胞毒性活性并且在特定刺激下不能产生IFNγ。因此，EBV 特异性排斥反应似乎在 NPC 肿瘤部位功能失活。
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 IFNγ upon specific stimulation. Thus, EBV-specific rejection responses appear to be functionally inactivated at the tumor site in NPC.
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影响因子：
5.4
作者：
Brooks, JM;Croom-Carter, DSG;Rickinson, AB
通讯作者：
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影响因子：
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