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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Wiebke Pruessmann
  • Julie Rytlewski
  • James Wilmott
  • Martin C. Mihm
  • Grace H. Attrill
  • Dyring-Andersen, Beatrice
  • 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

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 beta-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.

Original languageEnglish
JournalNature cancer
Volume1
Issue number2
Pages (from-to)197-209
Number of pages26
DOIs
Publication statusPublished - 2020
Externally publishedYes

    Research areas

  • TUMOR-INFILTRATING LYMPHOCYTES, CUTANEOUS MELANOMA, MALIGNANT-MELANOMA, PROGNOSTIC VALUE, CTLA-4 BLOCKADE, NODE STATUS, SURVIVAL, IPILIMUMAB, PREDICTION, CANCER

ID: 257193047