Characterization of Distinct T Cell Receptor Repertoires in Tumor and Distant Non-tumor Tissues from Lung Cancer Patients

被引:24
作者
Wang, Xiang [1 ,2 ]
Zhang, Botao [1 ,2 ]
Yang, Yikun [2 ,3 ]
Zhu, Jiawei [2 ,3 ]
Cheng, Shujun [2 ,3 ]
Mao, Yousheng [2 ,3 ]
Feng, Lin [1 ,2 ]
Xiao, Ting [1 ,2 ]
机构
[1] Chinese Acad Med Sci, State Key Lab Mol Oncol, Dept Etiol & Carcinogenesis, Natl Canc Ctr,Natl Clin Res Ctr Canc,Canc Hosp, Beijing 100021, Peoples R China
[2] Peking Union Med Coll, Beijing 100021, Peoples R China
[3] Chinese Acad Med Sci, Dept Thorac Surg, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, Beijing 100021, Peoples R China
关键词
Adaptive immune response; T cell receptor repertoire; Lung cancer; High-throughput sequencing; TCR diversity; INTRATUMOR HETEROGENEITY; INFILTRATING LYMPHOCYTES; DIVERSITY; SEQUENCE; DEEP; GENERATION; COMPLEXITY; REVEALS; AGE;
D O I
10.1016/j.gpb.2018.10.005
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
T cells and T cell receptors (TCRs) play pivotal roles in adaptive immune responses against tumors. The development of next-generation sequencing technologies has enabled the analysis of the TCR beta repertoire usage. Given the scarce investigations on the TCR repertoire in lung cancer tissues, in this study, we analyzed TCR beta repertoires in lung cancer tissues and the matched distant non-tumor lung tissues (normal lung tissues) from 15 lung cancer patients. Based on our results, the general distribution of T cell clones was similar between cancer tissues and normal lung tissues; however, the proportion of highly expanded clones was significantly higher in normal lung tissues than in cancer tissues (0.021% +/- 0.002% vs. 0.016% +/- 0.001%, P = 0.0054, Wilcoxon signed rank test). In addition, a significantly higher TCR diversity was observed in cancer tissues than in normal lung tissues (431.37 +/- 305.96 vs. 166.20 +/- 101.58, P = 0.0075, Mann-Whitney U test). Moreover, younger patients had a significantly higher TCR diversity than older patients (640.7 +/- 295.3 vs. 291.8 +/- 233.6, P=0.036, Mann-Whitney U test), and the higher TCR diversity in tumors was significantly associated with worse cancer outcomes. Thus, we provided a comprehensive comparison of the TCR repertoires between cancer tissues and matched normal lung tissues and demonstrated the presence of distinct T cell immune microenvironments in lung cancer patients.
引用
收藏
页码:287 / 296
页数:10
相关论文
共 33 条
  • [1] Characteristics of Tumor Infiltrating Lymphocyte and Circulating Lymphocyte Repertoires in Pancreatic Cancer by the Sequencing of T Cell Receptors
    Bai, Xueli
    Zhang, Qi
    Wu, Song
    Zhang, Xiaoyu
    Wang, Mingbang
    He, Fusheng
    Wei, Tao
    Yang, Jiaqi
    Lou, Yu
    Cai, Zhiming
    Liang, Tingbo
    [J]. SCIENTIFIC REPORTS, 2015, 5
  • [2] Trimmomatic: a flexible trimmer for Illumina sequence data
    Bolger, Anthony M.
    Lohse, Marc
    Usadel, Bjoern
    [J]. BIOINFORMATICS, 2014, 30 (15) : 2114 - 2120
  • [3] Bolotin DA, 2013, NAT METHODS, V10, P813, DOI [10.1038/nmeth.2555, 10.1038/NMETH.2555]
  • [4] Age-Related Decrease in TCR Repertoire Diversity Measured with Deep and Normalized Sequence Profiling
    Britanova, Olga V.
    Putintseva, Ekaterina V.
    Shugay, Mikhail
    Merzlyak, Ekaterina M.
    Turchaninova, Maria A.
    Staroverov, Dmitriy B.
    Bolotin, Dmitriy A.
    Lukyanov, Sergey
    Bogdanova, Ekaterina A.
    Mamedov, Ilgar Z.
    Lebedev, Yuriy B.
    Chudakov, Dmitriy M.
    [J]. JOURNAL OF IMMUNOLOGY, 2014, 192 (06) : 2689 - 2698
  • [5] High-throughput T cell receptor sequencing reveals distinct repertoires between tumor and adjacent non-tumor tissues in HBV-associated HCC
    Chen, Yunqing
    Xu, Ying
    Zhao, Miaoxian
    Liu, Yu
    Gong, Mingxing
    Xie, Cantao
    Wu, Hongkai
    Wang, Zhanhui
    [J]. ONCOIMMUNOLOGY, 2016, 5 (10):
  • [6] T cell receptor β-chain repertoire analysis reveals intratumour heterogeneity of tumour-infiltrating lymphocytes in oesophageal squamous cell carcinoma
    Chen, Zengchao
    Zhang, Chaoting
    Pan, Yaqi
    Xu, Ruiping
    Xu, Changqing
    Chen, Ziping
    Lu, Zheming
    Ke, Yang
    [J]. JOURNAL OF PATHOLOGY, 2016, 239 (04) : 450 - 458
  • [7] Functional Development of the T Cell Receptor for Antigen
    Ebert, Peter J. R.
    Li, Qi-Jing
    Huppa, Johannes B.
    Davis, Mark M.
    [J]. DEVELOPMENT OF T CELL IMMUNITY, 2010, 92 : 65 - 100
  • [8] How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine
    Gerlinger, M.
    Swanton, C.
    [J]. BRITISH JOURNAL OF CANCER, 2010, 103 (08) : 1139 - 1143
  • [9] Ultra-deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas
    Gerlinger, Marco
    Quezada, Sergio A.
    Peggs, Karl S.
    Furness, Andrew J. S.
    Fisher, Rosalie
    Marafioti, Teresa
    Shende, Vishvesh H.
    McGranahan, Nicholas
    Rowan, Andrew J.
    Hazell, Steven
    Hamm, David
    Robins, Harlan S.
    Pickering, Lisa
    Gore, Martin
    Nicol, David L.
    Larkin, James
    Swanton, Charles
    [J]. JOURNAL OF PATHOLOGY, 2013, 231 (04) : 424 - 432
  • [10] Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
    Gerlinger, Marco
    Rowan, Andrew J.
    Horswell, Stuart
    Larkin, James
    Endesfelder, David
    Gronroos, Eva
    Martinez, Pierre
    Matthews, Nicholas
    Stewart, Aengus
    Tarpey, Patrick
    Varela, Ignacio
    Phillimore, Benjamin
    Begum, Sharmin
    McDonald, Neil Q.
    Butler, Adam
    Jones, David
    Raine, Keiran
    Latimer, Calli
    Santos, Claudio R.
    Nohadani, Mahrokh
    Eklund, Aron C.
    Spencer-Dene, Bradley
    Clark, Graham
    Pickering, Lisa
    Stamp, Gordon
    Gore, Martin
    Szallasi, Zoltan
    Downward, Julian
    Futreal, P. Andrew
    Swanton, Charles
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (10) : 883 - 892