The co-evolving tumour cells and the systemic immune environment are mutually dysregulated. Tumours affect the immune response in a complex manner. For example, although lymphocytes are mobilized in response to tumours, their function is impaired by tumour progression. This study aimed to explore how the baseline and dynamic renal cell carcinoma (RCC) tumour burdens affect the T-cell repertoire, and whether the baseline T-cell receptor β-chain (TCRB) diversity predicts prognosis. To characterise the TCRB repertoire, the baseline and follow-up peripheral TCRB repertoires of 45 patients with RCC and 2 patients with benign renal disease patients were examined using high-throughput TCRB sequencing. To explain the significance of TCRB diversity, 56 peripheral leukocyte samples from 28 patients before and after surgery were subjected to transcriptome sequencing. To validate the results, an advanced RCC patient's sample was subjected to single-cell RNA sequencing (scRNA, 10x Genomics). Higher TCRB diversity was found to be correlated with a higher lymphocyte-to-neutrophil ratio, especially indicating more naïve T cells. High-baseline TCRB diversity predicted a better prognosis for stage IV patients, and different tumour burdens exerted distinct effects on the immune status. The pre-operative TCRB diversity was significantly higher in benign and stage I (low tumour burden) RCC patients than in stage IV (high tumour burden) patients. After the tumour burden of advanced patients was mostly relieved, we observed that the TCRB diversity was restored, T-cell exhaustion was reduced, and naïve T-cells were mobilized. It was demonstrated that the circulating TCRB repertoire could reflect the immune status and predict prognosis, and to some extent that cytoreductive nephrectomy (CN) reduces the burden of the immune system in advanced patients, which might provide a good opportunity for immunotherapy. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

中文翻译：

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肾细胞癌患者 TCR 谱分析的特征、动态变化和预后意义。

共同进化的肿瘤细胞和全身免疫环境相互失调。肿瘤以复杂的方式影响免疫反应。例如，尽管淋巴细胞在响应肿瘤时被动员，但它们的功能会因肿瘤进展而受损。本研究旨在探讨基线和动态肾细胞癌 (RCC) 肿瘤负荷如何影响 T 细胞库，以及基线 T 细胞受体 β 链 (TCRB) 多样性是否可以预测预后。为了表征 TCRB 库，使用高通量 TCRB 测序检查了 45 名 RCC 患者和 2 名良性肾病患者的基线和随访外周 TCRB 库。为了解释 TCRB 多样性的重要性，我们对 28 名患者手术前后的 56 份外周血白细胞样本进行了转录组测序。为了验证结果，对晚期 RCC 患者的样本进行了单细胞 RNA 测序（scRNA，10x Genomics）。研究发现较高的 TCRB 多样性与较高的淋巴细胞与中性粒细胞比率相关，尤其表明更多的初始 T 细胞。高基线 TCRB 多样性预示着 IV 期患者更好的预后，不同的肿瘤负荷对免疫状态产生不同的影响。良性和 I 期（低肿瘤负荷）RCC 患者的术前 TCRB 多样性显着高于 IV 期（高肿瘤负荷）患者。在晚期患者的肿瘤负担大部分减轻后，我们观察到TCRB多样性恢复，T细胞耗竭减少，幼稚T细胞被动员起来。结果表明，循环TCRB库可以反映免疫状态并预测预后，细胞减灭性肾切除术（CN）在一定程度上减轻了晚期患者免疫系统的负担，这可能为免疫治疗提供了良好的机会。© 2020 作者。《病理学杂志》由 John Wiley & Sons Ltd 代表大不列颠及爱尔兰病理学会出版。