High-throughput T cell receptor sequencing reveals distinct repertoires between tumor and adjacent non-tumor tissues in HBV-associated HCC
High-throughput T cell receptor sequencing reveals distinct repertoires between tumor and adjacent non-tumor tissues in HBV-associated HCC
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高通量 T 细胞受体测序揭示了 HBV 相关 HCC 中肿瘤组织和邻近非肿瘤组织之间的独特特性
DOI：
10.1080/2162402x.2016.1219010
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发表时间：
2016-01-01
期刊：
影响因子：
7.2
通讯作者：
Wang, Zhanhui
中科院分区：
文献类型：
--
作者：
Chen, Yunqing;Xu, Ying;Wang, Zhanhui
T淋巴细胞通过特异性T细胞受体（TCRs）识别抗原肽，在人体适应性免疫应答中发挥重要作用。TCR多样性与宿主免疫反应和肿瘤预后密切相关。尽管肿瘤浸润性T淋巴细胞对肿瘤预后有影响，但很少有研究对乙型肝炎病毒（HBV）相关肝细胞癌（HCC）肿瘤和非肿瘤组织中TCR多样性进行详细表征。在这里，我们对48例hbv相关HCC患者肝浸润T细胞的TCRβ链互补决定区3 （CDR3）进行了高通量测序。肿瘤组织中cdr3aa克隆型的平均数量（2259比1324，p < 0.001）和TCR多样性（Gini系数，p < 0.001； Simpson指数，p < 0.01； Shannon熵，p < 0.001）均显著高于邻近非肿瘤组织。当HEC阈值大于等于2%时，非肿瘤组织中高度扩增克隆（HEC）的比例显著高于肿瘤组织（p < 0.05）。我们对中位Morisita-Horn指数的分析表明，肿瘤和匹配的非肿瘤组织之间的TCR库相似性较弱。每位患者肿瘤组织和匹配的非肿瘤组织中共享克隆数的中位数为360.5个，占每位患者所有克隆的5.1-15.8%（10.6±0.4%）。我们观察到肿瘤中T淋巴细胞的广泛异质性和HCC患者邻近非肿瘤组织中较高的HEC比率。肿瘤和非肿瘤组织中不同的T细胞谱提示hbv相关HCC患者存在不同的T细胞免疫微环境。
ABSTRACT T lymphocytes, which recognize antigen peptides through specific T cell receptors (TCRs), play an important role in the human adaptive immune response. TCR diversity is closely associated with host immune response and cancer prognosis. Although tumor-infiltrating T lymphocytes have implications for tumor prognosis, few studies have performed a detailed characterization of TCR diversity in both tumor and non-tumor tissues in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Here, we performed high-throughput sequencing of the TCRβ chain complementarity determining region 3 (CDR3) of liver-infiltrating T cells from 48 HBV-associated HCC patients. A significantly higher average number of CDR3 aa clonotypes (2259 vs. 1324, p < 0.001), and significantly higher TCR diversity (Gini coefficient, p < 0.001; Simpson index, p < 0.01; Shannon entropy, p < 0.001) were observed in tumor tissues compared with adjacent non-tumor tissues. The ratio of highly expanded clones (HECs) was significantly higher in non-tumor tissues than in tumor tissues when the HEC threshold was defined as 2% or greater (p < 0.05). Our analysis of the median Morisita-Horn index indicated weak TCR repertoire similarity between tumor and matched non-tumor tissues. The median number of shared clones in tumor tissue and matched non-tumor tissue from each patient was 360.5, representing 5.1–15.8% (10.6 ± 0.4%) of all clones in each patient. We observed extensive heterogeneity of T lymphocytes in tumors and higher HEC ratios in adjacent non-tumor tissues of HCC patients. The differential T cell repertoires in tumor and non-tumor tissues suggest a distinct T cell immune microenvironment in patients with HBV-associated HCC.