Diversity index of mucosal resident T lymphocyte repertoire predicts clinical prognosis in gastric cancer

Diversity index of mucosal resident T lymphocyte repertoire predicts clinical prognosis in gastric cancer
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DOI:
10.1080/2162402x.2014.1001230
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发表时间:
2015-01-01
期刊:
影响因子:
7.2
通讯作者:
Wan, Ying
Wan, Ying
中科院分区:
医学2区
文献类型:
--
作者:
Jia, Qingzhu;Zhou, Junfeng;Wan, Ying

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人类癌症的特征性免疫病理学是在实体瘤组织内诱导肿瘤抗原特异性T淋巴细胞应答。目前的免疫监测策略集中在肿瘤浸润性T淋巴细胞的密度和分化状态的定量;然而,TCR库的性质。包括抗原特异性、克隆性以及其预后意义。仍然难以捉摸在这项研究中,我们招募了28名胃癌患者,并收集了肿瘤组织、邻近正常粘膜组织和外周血样本,以通过深度测序分析研究这些患者TCR β库的景观和区室化。我们的研究结果说明了抗原驱动的扩张内的肿瘤室和收缩的大小共享克隆型粘膜和外周血。最重要的是,粘膜T淋巴细胞的多样性可以独立地预测预后,这强烈强调了驻留粘膜T细胞在执行术后免疫监视以防止肿瘤复发中的关键作用。
A characteristic immunopathology of human cancers is the induction of tumor antigen-specific T lymphocyte responses within solid tumor tissues. Current strategies for immune monitoring focus on the quantification of the density and differentiation status of tumor-infiltrating T lymphocytes; however, properties of the TCR repertoire. including antigen specificity, clonality, as well as its prognostic significance. remain elusive. In this study, we enrolled 28 gastric cancer patients and collected tumor tissues, adjacent normal mucosal tissues, and peripheral blood samples to study the landscape and compartmentalization of these patients' TCR beta repertoire by deep sequencing analyses. Our results illustrated antigen-driven expansion within the tumor compartment and the contracted size of shared clonotypes in mucosa and peripheral blood. Most importantly, the diversity of mucosal T lymphocytes could independently predict prognosis, which strongly underscores critical roles of resident mucosal T-cells in executing postsurgery immunosurveillance against tumor relapse.