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阴茎癌中 T 细胞受体库的特征分析

英文原题:Characterization of T cell receptor repertoire in penile cancer.

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Characterization of T cell receptor repertoire in penile cancer.

PubMed 2024/01/27(内容时间) Cancer Immunol Immunother Q1 · IF 5.8(JCR 2025)

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中文摘要

TIL(肿瘤浸润淋巴细胞)(TILs)在调节宿主免疫应答和塑造肿瘤微环境中发挥关键作用。此前已有研究表明,阴茎肿瘤中的T细胞浸润与临床结局相关。

然而,很少有研究报道阴茎癌患者的T细胞受体(TCR)库。在本研究中,我们评估了22例阴茎鳞状细胞癌(PSCC)患者肿瘤及癌旁正常组织中的TCR库。对T细胞受体β可变(TRBV)和连接(TRBJ)基因使用的分析以及互补决定区3(CDR3)长度分布的分析未显示肿瘤与配对正常组织之间存在显著差异。

此外,中位Jaccard指数的分析表明这些组之间TCR库的重叠有限。与正常组织相比,肿瘤样本中观察到TCR库多样性显著降低且克隆性显著升高,这与临床特征相关。对转录谱的进一步分析表明,高克隆性的肿瘤样本中与CD8+ 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CD4+ T细胞和CD8+ T细胞的TCR库。我们发现扩增的克隆型主要存在于CD8+ T细胞区室中,并呈现耗竭表型。

总体而言,我们全面比较了阴茎肿瘤与正常组织之间的TCR库,并证明了PSCC患者中存在不同的T细胞免疫微环境。

展开英文摘要原文

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.

论文信息

作者
Zhang J、Wang Y、Huang Y、Tan X、Xu J、Yan Q、Tan J、Zhang Y
第一作者单位
Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing, 401331, People's Republic of China.China
通讯作者单位
Department of Urology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China. doclan@yeah.net.China
期刊
Cancer immunology, immunotherapy : CII2024 Jan 27
原文标识
PubMed 38280010 · DOI 10.1007/s00262-023-03615-z