Characterization of T cell receptor repertoire in penile cancer.
Characterization of T cell receptor repertoire in penile cancer.
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DOI：
10.1007/s00262-023-03615-z
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发表时间：
2024-01-27
影响因子：
5.8
通讯作者：
Lan, Weihua
中科院分区：
文献类型：
--
作者：
Zhang, Junying;Wang, Yapeng;Huang, Yiqiang;Tan, Xintao;Xu, Jing;Yan, Qian;Tan, Jiao;Zhang, Yao;Zhang, Jun;Ma, Qiang;Zhu, Hailin;Ye, Jin;Zhu, Zhaojing;Lan, Weihua
肿瘤浸润淋巴细胞（TIL）在调节宿主免疫反应和塑造肿瘤微环境中起着关键作用。先前已经表明，阴茎肿瘤中的T细胞浸润与临床结果相关。然而，很少有研究报道阴茎癌患者的T细胞受体（TCR）库。本研究对22例阴茎鳞状细胞癌（PSCC）患者的肿瘤组织及癌旁正常组织中的TCR进行了检测。对T细胞受体β-可变区（TRBV）和连接区（TRBJ）基因使用情况的分析以及对互补决定区3（CDR 3）长度分布的分析未显示肿瘤和匹配的正常组织之间存在显著差异。此外，中值Jaccard指数的分析表明这些组之间TCR库的有限重叠。与正常组织相比，肿瘤组织中TCR库的多样性明显降低，克隆性升高，这与临床特征有关。转录谱的进一步分析表明，具有高克隆性的肿瘤样品显示与CD 8 + T细胞相关的基因表达增加。此外，我们分析了从肿瘤组织中分离的CD 4 + T细胞和CD 8 + T细胞的TCR库。我们鉴定出扩增的克隆型主要在CD 8 + T细胞区室中，其呈现耗尽的表型。总的来说，我们全面比较了阴茎肿瘤和正常组织之间的TCR库，并证明了PSCC患者存在不同的T细胞免疫微环境。在线版本包含补充材料，可通过10.1007/s 00262 -023-03615-z获得。
Tumor-infiltrating lymphocytes (TILs) play a key role in regulating the host immune response and shaping tumor microenvironment. It has been previously shown that T cell infiltration in penile tumors was associated with clinical outcomes. However, few studies have reported the T cell receptor (TCR) repertoire in patients with penile cancer. In the present study, we evaluated the TCR repertoires in tumor and adjacent normal tissues from 22 patients with penile squamous cell carcinoma (PSCC). Analysis of the T cell receptor beta-variable (TRBV) and joining (TRBJ) genes usage and analysis of complementarity determining region 3 (CDR3) length distribution did not show significant differences between tumor and matched normal tissues. Moreover, analysis of the median Jaccard index indicated a limited overlap of TCR repertoire between these groups. Compared with normal tissues, a significantly lower diversity and higher clonality of TCR repertoire was observed in tumor samples, which was associated with clinical characteristics. Further analysis of transcriptional profiles demonstrated that tumor samples with high clonality showed increased expression of genes associated with CD8 + T cells. In addition, we analyzed the TCR repertoire of CD4 + T cells and CD8 + T cells isolated from tumor tissues. We identified that expanded clonotypes were predominantly in the CD8 + T cell compartment, which presented with an exhausted phenotype. Overall, we comprehensively compared TCR repertoire between penile tumor and normal tissues and demonstrated the presence of distinct T cell immune microenvironments in patients with PSCC. The online version contains supplementary material available at 10.1007/s00262-023-03615-z.
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