Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence
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Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence. / Pruessmann, Wiebke; Rytlewski, Julie; Wilmott, James; Mihm, Martin C.; Attrill, Grace H.; Dyring-Andersen, Beatrice; Fields, Paul; Zhan, Qian; Colebatch, Andrew J.; Ferguson, Peter M.; Thompson, John F.; Kallenbach, Klaus; Yusko, Erik; Clark, Rachael A.; Robins, Harlan; Scolyer, Richard A.; Kupper, Thomas S.
In: Nature cancer, Vol. 1, No. 2, 2020, p. 197-209.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence
AU - Pruessmann, Wiebke
AU - Rytlewski, Julie
AU - Wilmott, James
AU - Mihm, Martin C.
AU - Attrill, Grace H.
AU - Dyring-Andersen, Beatrice
AU - Fields, Paul
AU - Zhan, Qian
AU - Colebatch, Andrew J.
AU - Ferguson, Peter M.
AU - Thompson, John F.
AU - Kallenbach, Klaus
AU - Yusko, Erik
AU - Clark, Rachael A.
AU - Robins, Harlan
AU - Scolyer, Richard A.
AU - Kupper, Thomas S.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - TUMOR-INFILTRATING LYMPHOCYTES
KW - CUTANEOUS MELANOMA
KW - MALIGNANT-MELANOMA
KW - PROGNOSTIC VALUE
KW - CTLA-4 BLOCKADE
KW - NODE STATUS
KW - SURVIVAL
KW - IPILIMUMAB
KW - PREDICTION
KW - CANCER
U2 - 10.1038/s43018-019-0019-5
DO - 10.1038/s43018-019-0019-5
M3 - Journal article
C2 - 33305293
VL - 1
SP - 197
EP - 209
JO - Nature cancer
JF - Nature cancer
IS - 2
ER -
ID: 257193047