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Abstract：
The T-cell immune responses in nasopharyngeal carcinoma patients have been extensively investigated recently for designing adoptive immunotherapy or immune checkpoint blockade therapy. However, the distribution characteristics of T cells associated with NPC pathogenesis are largely unknown. We performed deep sequencing for TCR repertoire profiling on matched tumor/adjacent normal tissue from 15 NPC patients and peripheral blood from 39 NPC patients, 39 patients with other nasopharyngeal diseases, and 33 healthy controls. We found that a lower diversity of TCR repertoire in tumors than paired tissues or a low similarity between the paired tissues was associated with a poor prognosis in NPC. A more diverse TCR repertoire was identified in the peripheral blood of NPC patients relative to the controls; this was related to a significant decrease in the proportion of high-frequency TCR clones in NPC. Higher diversity in peripheral blood of NPC patients was associated with a worse prognosis. Due to the peculiarity of the Vβ gene usage patterns in the peripheral blood of NPC patients, 15 Vβ genes were selected to distinguish NPC patients from controls by the least absolute shrinkage and selection operator analysis. We identified 11 clonotypes shared by tumors and peripheral blood samples from different NPC patients, defined as \"NPC-associated\" that might have value in adoptive immunotherapy. In conclusion, we here report the systematic and overall characteristics of the TCR repertoire in tumors, adjacent normal tissues, and peripheral blood of NPC patients. The data obtained may be relevant to future clinical studies in the setting of immunotherapy for NPC patients.
摘要：
最近，针对鼻咽癌患者的T细胞免疫反应进行了广泛的研究，以设计过继免疫疗法或免疫检查点阻断疗法。然而,与NPC发病相关的T细胞的分布特征尚不清楚。我们对来自15例NPC患者的匹配肿瘤/邻近正常组织和来自39例NPC患者的外周血进行了TCR库谱分析的深度测序，39例其他鼻咽疾病患者，和33个健康对照。我们发现，与配对组织相比，肿瘤中TCR库的多样性较低或配对组织之间的相似性较低与NPC的预后不良有关。与对照组相比，在NPC患者的外周血中发现了更多样化的TCR库；这与NPC中高频TCR克隆的比例显着下降有关。鼻咽癌患者外周血较高的多样性与预后较差有关。由于鼻咽癌患者外周血中Vβ基因使用模式的特殊性,通过最小绝对收缩和选择操作员分析，选择了15个Vβ基因来区分NPC患者与对照组。我们确定了来自不同NPC患者的肿瘤和外周血样本共有的11个克隆型，定义为“NPC相关”，可能在过继免疫疗法中具有价值。总之,我们在这里报道了肿瘤中TCR库的系统和整体特征，邻近的正常组织，和NPC患者的外周血。获得的数据可能与NPC患者免疫治疗的未来临床研究有关。
