Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence

原发性黑色素瘤 T 细胞的分子分析可识别有转移性复发风险的患者

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作者:Wiebke Pruessmann #, Julie Rytlewski #, James Wilmott #, Martin C Mihm Jr, Grace H Attrill, Beatrice Dyring-Andersen, Paul Fields, Qian Zhan, Andrew J Colebatch, Peter M Ferguson, John F Thompson, Klaus Kallenbach, Erik Yusko, Rachael A Clark, Harlan Robins, Richard A Scolyer #, Thomas S Kupper #

Abstract

Primary melanomas >1 mm thickness are potentially curable by resection, but can recur metastatically. We assessed the prognostic value of T cell fraction (TCFr) and repertoire T cell clonality, measured by high-throughput-sequencing of the T cell receptor beta chain (TRB) in T2-T4 primary melanomas (n=199). TCFr accurately predicted progression-free survival (PFS) and was independent of thickness, ulceration, mitotic rate, or age. TCFr was second only to tumor thickness in its predictive value, using a gradient boosted model. For accurate PFS 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. This study suggests that a successful T cell-mediated antitumor response can be present in primary melanomas.

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