[1]罗　磊,岳小变,赵宏峰,等.乙型肝炎病毒性相关性肝细胞癌患者外周血与肝癌组织T淋巴细胞受体谱系分析[J].新乡医学院学报,2016,33(8):686-691.[doi:10.7683/xxyxyxb.2016.08.010]
　LUO Lei,YUE Xiao-bian,ZHAO Hong-feng,et al.Analysis of T cell receptor repertoire diversity in peripheral blood lymphocytes and tumor-infiltrating T lymphocytes of patients with hepatitis B Virus related hepatocellular carcinoma[J].Journal of Xinxiang Medical University,2016,33(8):686-691.[doi:10.7683/xxyxyxb.2016.08.010]
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乙型肝炎病毒性相关性肝细胞癌患者外周血与肝癌组织T淋巴细胞受体谱系分析
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
33
期数:
2016年8
页码:
686-691
栏目:
临床研究
出版日期:
2016-07-27

文章信息/Info

Title:
Analysis of T cell receptor repertoire diversity in peripheral blood lymphocytes and tumor-infiltrating T lymphocytes of patients with hepatitis B Virus related hepatocellular carcinoma
作者:
罗　磊1; 岳小变2; 赵宏峰3; 王天宝1; 孙雯雯1; 张光文1
（1.新乡医学院第一附属医院感染内二科，河南　卫辉　453100；2.漯河医学高等专科学校第二附属医院ICU，河南　漯河　462000；3.新乡市中心医院肿瘤外科，河南　新乡　453000）
Author(s):
LUO Lei1; YUE Xiao-bian2; ZHAO Hong-feng3; WANG Tian-bao1; SUN Wen-wen1; ZHANG Guang-wen1
（1.Department of Infectious Diseases，the First Affiliated Hospital of Xinxiang Medical University，Weihui 453100，Henan Province，China；2.Intensive Care Units，the Second Affiliated Hospital of Luohe Medical College，Luohe 462000，Henan Province，China；3.Department of Oncological Surgery，the Central Hospital of Xinxiang City，Xinxiang 453000，Henan Province，China）
关键词:
乙型病毒肝炎相关性肝细胞癌; 肿瘤浸润性T淋巴细胞; T细胞受体; 互补决定区3
Keywords:
hepatitis B virus related hepatocellular carcinoma; tumor-infiltrating T lymphocytes; T cell receptor; complementarity determining 3
分类号:
R512.6+2
DOI:
10.7683/xxyxyxb.2016.08.010
文献标志码:
A
摘要:
目的　比较乙型肝炎病毒性相关性肝细胞癌（HBV-RHCC）患者外周血T淋巴细胞（PBLs）与肝癌组织中浸润性T淋巴细胞（TILs）受体（TCR）谱系及互补决定区3（CDR3）序列特点。方法　选择新乡市中心医院2014年3~8月行肝癌切除术患者10例为研究对象。应用反转录-聚合酶链反应（RT-PCR）扩增TCRβ链可变区（BV）中CDR3基因的24个家族，采用扭曲率、缺失率、正态率、单峰率以及复杂评分分析TCR-BV各家族谱系的完整性与多样性，并将优势利用的谱系家族进行CDR3测序。结果　10例HBV-RHCC患者CDR3谱系多数呈现扭曲分布。PBLs与TILs复合评分比较差异有统计学意义（P=0.042）；且上述谱系特征与肝癌家族史、AFP水平有关，但与患者的病毒载量无关。此外，在PBLs与TILs中发现了“GGTGVSPLH”“LGTGNDDPF”共有序列。结论　HBV-RHCC患者PBLs与TILs中存在克隆性增生，并证实了局部细胞免疫功能差异的存在。多个共有序列的发现，为HBV-RHCC的靶向治疗提供理论基础与潜在的靶点。
Abstract:
Objective　To compare the feature of T cell receptor（TCR）repertoire diversity and complementarity determining region3（CDR3） sequences in peripheral blood lymphocytes（PBLs） and tumor-Infiltrating T lymphocytes（TILs） of the patients with hepatitis B Virus related hepatocellular carcinoma（HBV-RHCC）.Methods　Ten patients with hepatectomy in the Central Hospital of Xinxiang City from March to August 2014 were selected.TCR-BV families were amplified by reverse transcription polymerase chain reaction and the repertoire diversity of BV families.Twist rate，miss rate，normal distribution rate，single rate and complexity scores were used to evaluate the integrity and diversity of TCR profile between PBLs and TILs.The clonally of the T cells was further analyzed by CDR3 sequencing.Results　A majority of the CDR3 profiles of PBLs and TILs in 10 HBV-RHCC patients showed a distorted distribution.There was significant difference in the complexity score of the profiles in TILs compared with PBLs compartment （P=0.042）.This pattern was respective related to family history of hepatocellular carcinoma and level of alpha-fetoprotein，with the exception of the patient′s HBV-DNA viral load.In addition，the consensus sequences "GGTGVSPLH" and "LGTGNDDPF" were found distributed between PBLs and TILs compartments in different patients.Conclusion　The study find an apparent clonal proliferation in PBLs and TILs compartments，and confirmed a remarkable difference in cellular immunology in PBLs and TILs.The relatively conserved amino acid motifs provide fundamental basis and could be a potential target for targeted therapy in HBV-RHCC patients.

参考文献/References:

［1］　JEMAL A，BRAY F，CENTER M M，et al.Global cancer statistics［J］.CA Cancer J Clin，2011，61（2）：69-90.
［2］　CUI Y，JIA J.Update on epidemiology of hepatitis B and C in China［J］.J Gastroenterol Hepatol，2013，28（Suppl 1）：7-10.
［3］　NEUVEUT C，WEI Y，BUENDIA M A.Mechanisms of HBV-related hepatocarcinogenesis［J］.J Hepatol，2010，52（4）：594-604.
［4］　PRENDERGAST G C，JAFFEE E M.Cancer immunologists and cancer biologists：why we didn′t talk then but need to now［J］.Cancer Res，2007，67（8）：3500-3504.
［5］　RUDENSKY A Y.Regulatory T cells and Foxp3［J］.Immunol Rev，2011，241（1）：260-268.
［6］　KUCZMA M，KOPIJ M，PAWLIKOWSKA I，et al.Intratumoral convergence of the TCR repertoires of effector and Foxp3+ CD4+T cells［J］.PLoS One，2010，5（10）：e13623.
［7］　CONDEELIS J，POLLARD J W.Macrophages：obligate partners for tumor cell migration，invasion，and metastasis［J］.Cell，2006，124（2）：263-266.
［8］　EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER,EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER.EASL-EORTC clinical practice guidelines：management of hepatocellular carcinoma［J］.J Hepatol，2012，56（4）：908-943.
［9］　YAO X S，ZHANG G W，MA L，et al.Analysis of the CDR3 length of TCR alphabeta T cells in the peripheral blood of patients with chronic hepatitis B［J］.Hepatol Res，2006，35（1）：10-18.
［10］　LU J，BASU A，MELENHORST J J，et al.Analysis of T-cell repertoire in hepatitis-associated aplastic anemia［J］.Blood，2004，103（12）：4588-4593.
［11］　ROWEN L，KOOP B F，HOOD L.The complete 685-kilobase DNA sequence of the human beta T cell receptor locus［J］.Science，1996，272（5269）：1755-1762.
［12］　PANNETIER C，EVEN J，KOURILSKY P.T-cell repertoire diversity and clonal expansions in normal and clinical samples［J］.Immunology Today，1995，16（4）：176-181.
［13］　GOODEN M J，DE BOCK G H，LEFFERS N，et al.The prognostic influence of tumour-infiltrating lymphocytes in cancer：a systematic review with meta-analysis［J］.Br J Cancer，2011，105（1）：93-103.
［14］　LUO W，LIAO W J，HUANG Y T，et al.Normalization of T cell receptor repertoire diversity in patients with advanced colorectal cancer who responded to chemotherapy［J］.Cancer Sci，2011，102（4）：706-712.
［15］　SORRENTINO C，MUSIANI P，POMPA P，et al.Androgen deprivation boosts prostatic infiltration of cytotoxic and regulatory T lymphocytes and has no effect on disease-free survival in prostate cancer patients［J］.Clin Cancer Res，2011，17（6）：1571-1581.
［16］　MA S W，LI Y Y，ZHANG G W，et al.Complementarity-determining region 3 size spectratypes of T cell receptor beta chains in CD8+T cells following antiviral treatment of chronic hepatitis B［J］.Antimicrob Agents Chemother，2011，55（2）：888-894.
［17］　SING G K，LI D，CHEN X，et al.A molecular comparison of T lymphocyte populations infiltrating the liver and circulating in the blood of patients with chronic hepatitis B：evidence for antigen-driven selection of a public complementarity-determining region 3 （CDR3） motif［J］.Hepatology，2001，33（5）：1288-1298.
［18］　WONG G L，CHAN H L，TSE Y K，et al.On-treatment alpha-fetoprotein is a specific tumor marker for hepatocellular carcinoma in patients with chronic hepatitis B receiving entecavir［J］.Hepatology，2014，59（3）：986-995.
［19］　DUDLEY M E，WUNDERLICH J R，ROBBINS P F，et al.Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes［J］.Science，2002，298（5594）：850-854.
［20］　SHERWOOD A M，EMERSON R O，SCHERER D，et al.Tumor-infiltrating lymphocytes in colorectal tumors display a diversity of T cell receptor sequences that differ from the T cells in adjacent mucosal tissue［J］.Cancer Immunol，2013，62（9）：1453-1461.
［21］　VENTURI V，PRICE D A，DOUEK D C，et al.The molecular basis for public T-cell responses［J］.Nat Rev Immunol，2008，8（3）：231-238.
［22］　KNOLLE P A，THIMME R.Hepatic immune regulation and its involvement in viral hepatitis infection［J］.Gastroenterology，2014，146（5）：1193-1207.

更新日期/Last Update: 2016-08-05