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鼻咽癌中EB病毒特异性T淋巴细胞的功能失活：对肿瘤免疫治疗的意义

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

作者信息

Li Jiang, 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

机构信息

State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.

出版信息

PLoS One. 2007 Nov 7;2(11):e1122. doi: 10.1371/journal.pone.0001122.

DOI:10.1371/journal.pone.0001122
PMID:17987110
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2048575/
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.

摘要

鼻咽癌（NPC）是一种与 Epstein-Barr 病毒（EBV）相关的恶性肿瘤，在中国南方地区高发。为了评估 EBV 特异性免疫缺陷是否可能导致肿瘤发生，对未经治疗的 NPC 患者的循环 T 细胞和肿瘤浸润淋巴细胞（TILs）的表型和功能进行了研究。与健康供体相比，患者循环中的初始 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。患者中识别 LMP1 和 LMP2 中七个 HLA-A2 限制性表位的 T 细胞频率较低，在用携带自体 EBV 的细胞刺激后仍保持较低水平。与外周血相比，低剂量 IL-2 扩增的 TILs 中 CD3+CD4+、CD3+CD45RO+和 CD4+CD25+细胞增加，LMP1 和 LMP2 四聚体阳性细胞频率高 2 至 5 倍。大多数患者血液中的 EBV 特异性细胞毒性可被重新激活，而 TILs 缺乏细胞毒性活性，在特异性刺激后不能产生 IFNγ。因此，在 NPC 肿瘤部位，EBV 特异性排斥反应在功能上似乎处于失活状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/cf5a8fc20bec/pone.0001122.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/6d581c3b4913/pone.0001122.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/050d2d7a50e6/pone.0001122.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/5bb25a171bea/pone.0001122.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/09c42a61c14e/pone.0001122.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/1571fd554f2b/pone.0001122.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/15ad076655ce/pone.0001122.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/cf5a8fc20bec/pone.0001122.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/6d581c3b4913/pone.0001122.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/050d2d7a50e6/pone.0001122.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/5bb25a171bea/pone.0001122.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/09c42a61c14e/pone.0001122.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/1571fd554f2b/pone.0001122.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/15ad076655ce/pone.0001122.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fb/2048575/cf5a8fc20bec/pone.0001122.g007.jpg

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