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Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence
Nature Cancer ( IF 22.7 ) Pub Date : 2020-01-20 , DOI: 10.1038/s43018-019-0019-5
Wiebke Pruessmann 1, 2 , Julie Rytlewski 3 , James Wilmott 4 , Martin C Mihm 1 , Grace H Attrill 4 , Beatrice Dyring-Andersen 1, 5 , Paul Fields 3 , Qian Zhan 1 , Andrew J Colebatch 4, 6 , Peter M Ferguson 4, 6 , John F Thompson 4, 7 , Klaus Kallenbach 8 , Erik Yusko 3 , Rachael A Clark 1 , Harlan Robins 3, 9 , Richard A Scolyer 4, 6 , Thomas S Kupper 1
Affiliation  

Primary melanomas >1 mm thickness are potentially curable by resection, but can recur metastatically. We assessed the prognostic value of the T-cell fraction (TCFr) and repertoire T-cell clonality, measured by high-throughput sequencing of the T-cell receptor β-chain in T2–T4 primary melanomas (n = 199). TCFr accurately predicted progression-free survival and was independent of thickness, ulceration, mitotic rate and age. TCFr was second only to tumor thickness in its predictive value, using a gradient-boosted model. For accurate progression-free survival prediction, adding TCFr to tumor thickness was superior to adding any other histopathological variable. Furthermore, a TCFr >20% was protective regardless of tumor ulceration status, mitotic rate or presence of nodal disease. TCFr is a quantitative molecular assessment that predicts metastatic recurrence in primary melanoma patients whose disease has been resected surgically. The present study suggests that a successful T-cell-mediated, antitumour response can be present in primary melanomas.



中文翻译:

原发性黑色素瘤 T 细胞的分子分析可识别有转移复发风险的患者

厚度>1毫米的原发性黑色素瘤可能可以通过切除治愈,但可能会转移性复发。我们评估了 T 细胞分数 (TCFr) 和全部 T 细胞克隆性的预后价值,通过对 T2-T4 原发性黑色素瘤 (n = 199) 中 T 细胞受体 β 链的高通量测序进行测量 。TCFr 准确预测无进展生存期,并且与厚度、溃疡、有丝分裂率和年龄无关。使用梯度增强模型,TCFr 的预测价值仅次于肿瘤厚度。为了准确预测无进展生存期,将 TCFr 添加到肿瘤厚度优于添加任何其他组织病理学变量。此外,无论肿瘤溃疡状态、有丝分裂率或是否存在淋巴结疾病,TCFr >20% 都具有保护作用。TCFr 是一种定量分子评估,可预测已手术切除的原发性黑色素瘤患者的转移复发。目前的研究表明,原发性黑色素瘤中可能存在成功的 T 细胞介导的抗肿瘤反应。

更新日期:2020-01-20
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