T cell receptor β-chain repertoire analysis reveals intratumour heterogeneity of tumour-infiltrating lymphocytes in oesophageal squamous cell carcinoma
T cell receptor β-chain repertoire analysis reveals intratumour heterogeneity of tumour-infiltrating lymphocytes in oesophageal squamous cell carcinoma
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DOI：
10.1002/path.4742
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发表时间：
2016-08-01
影响因子：
7.3
通讯作者：
Ke, Yang
中科院分区：
文献类型：
--
作者：
Chen, Zengchao;Zhang, Chaoting;Ke, Yang
由于缺乏有效的治疗方法，食管鳞状细胞癌（ESCC）的预后普遍较差。基于肿瘤浸润淋巴细胞（TIL）的免疫治疗方法已经证明，一些实体瘤患者可以产生持久的反应，这表明食管鳞癌免疫治疗临床应用的潜在可行性。然而，人们对 ESCC 中 TIL 的许多基本特征知之甚少，包括 TIL 反应的克隆性、特异性和空间异质性，这取决于抗原和 T 细胞受体 (TCR) 之间的相互作用。我们使用 TCR β 链 (TCR beta) 重排基因的超深度测序来分析肿瘤组织（每个肿瘤的 4 至 6 个区域）以及 7 名诊断为原发性 ESCC 患者的匹配的邻近正常组织和外周血中 T 细胞的基本特征。我们发现食管鳞癌内的T细胞克隆与外周血甚至邻近正常组织的T细胞克隆有很大不同。尽管肿瘤内 TCR β 库的重叠程度比肿瘤和其他组织之间的重叠程度相对较高，但肿瘤内 TCR β 库在空间上存在异质性。由于采样有限，高通量 TCR β 测序可以表征任何个体 ESCC 中相应 T 细胞克隆的有限（区室依赖性）部分的多样性和组成，扩大我们对免疫行为和免疫反应的理解，并为 ESCC 免疫治疗提供更多启示。版权所有 (C) 2016 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
Oesophageal squamous cell carcinoma (ESCC) has a generally poor prognosis, due to the lack of effective treatment methods. Immunotherapeutic approaches based on tumour-infiltrating lymphocytes (TILs) have demonstrated that durable responses are produced in some patients with solid tumours, which suggests the potential feasibility of clinical application of immunotherapy for ESCC. However, many of the basic characteristics of TILs in ESCC are poorly understood, including clonality, specificity and spatial heterogeneity of the response of TILs, which depends on the interaction between antigens and T cell receptors (TCRs). We used ultra-deep sequencing of rearranged genes in TCR beta-chain (TCR beta) to profile the basic characteristics of T cells in tumour tissues (four to six regions from each tumour) as well as matched adjacent normal tissue and peripheral blood from seven patients diagnosed with primary ESCC. We found that T cell clones within ESCCs were quite different from those of the peripheral blood and even the adjacent normal tissues in general. Although there was a relatively higher degree of overlap of intratumoural TCR beta repertoires than those between the tumour and other tissues, intratumoural TCR beta repertoires were spatially heterogeneous. Due to the restricted sampling, high-throughput TCR beta sequencing could characterize the diversity and composition of a limited (compartment-dependent) fraction of the respective T cell clones in any individual ESCC, expanding our understanding of immune behaviour and immune response and shedding more light on ESCC immunotherapy. Copyright (C) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.