The First Affiliated Hospital, Zhejiang University School of Medicine, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Hangzhou, China.
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Cancer Med. 2024 Aug;13(16):e70121. doi: 10.1002/cam4.70121.
In this study, we comprehensively profiled the T-cell receptor (TCR) repertoire of the tumor and adjacent normal tissue in patients with HBV-associated hepatocellular carcinoma (HCC) and determined the baseline characteristics and clinical significance of TCR.
High-throughput sequencing was used to determine the profile of complementarity-determining region 3 (CDR3) of the TCR-β chain variable (TRBV) in the tumor and normal tissue samples of 14 HCC patients. At the same time, TRBV diversity and differences in expression between tumor and normal tissues were investigated. The cumulative frequency of top 100 CDR3 (CF100), clonality, and Shannon entropy as indices to evaluate diversity, RESULTS: The diversity of TRBV CDR3 showed no significant difference between tumor and normal tissues. Of the 58 V gene segments in TRBV, TRBV16 and TRBV7-6 had a significantly higher frequency in the tumor group than in the normal group (p < 0.05). The frequency of 14 J gene segments showed no significant difference between tumor and normal tissues. In contrast, the frequency of 22 TRBVx/BJx combinations was significantly higher in the tumor than in the normal tissue. In addition, the length and type of TRBV CDR3 were similar in tumor and normal tissues, and a Gaussian distribution was observed in both groups.
This study provided a large amount of information about the TCR lineage in HBV-associated HCC, laying the foundation for further research. In addition, the fact that the immune repertoire (TRBV CDR3) hardly differs between tumor and adjacent normal tissue provides a new clue for exploring the mechanism of the liver as an organ with immune privileges.
在这项研究中,我们全面描绘了乙型肝炎病毒(HBV)相关肝细胞癌(HCC)患者肿瘤和相邻正常组织中的 T 细胞受体(TCR)谱,并确定了 TCR 的基线特征和临床意义。
采用高通量测序技术测定 14 例 HCC 患者肿瘤和正常组织样本中 TCR-β 链可变区(TRBV)互补决定区 3(CDR3)的谱。同时,研究了肿瘤和正常组织中 TRBV 多样性和表达差异。采用累积频率最高的前 100 个 CDR3(CF100)、克隆性和香农熵作为评估多样性的指标。
TRBV CDR3 的多样性在肿瘤和正常组织之间无显著差异。在 58 个 TRBV V 基因片段中,TRBV16 和 TRBV7-6 在肿瘤组中的频率明显高于正常组(p<0.05)。14 个 J 基因片段的频率在肿瘤和正常组织之间无显著差异。相比之下,22 个 TRBVx/BJx 组合在肿瘤中的频率明显高于正常组织。此外,肿瘤和正常组织中 TRBV CDR3 的长度和类型相似,两组均呈正态分布。
本研究为进一步研究 HBV 相关 HCC 中的 TCR 谱系提供了大量信息。此外,肿瘤和相邻正常组织之间免疫受体(TRBV CDR3)几乎没有差异,这为探索肝脏作为具有免疫特权的器官的机制提供了新线索。