PMID- 33305293 OWN - NLM STAT- MEDLINE DCOM- 20220414 LR - 20231010 IS - 2662-1347 (Electronic) IS - 2662-1347 (Linking) VI - 1 IP - 2 DP - 2020 Feb TI - Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence. PG - 197-209 LID - 10.1038/s43018-019-0019-5 [doi] AB - 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. FAU - Pruessmann, Wiebke AU - Pruessmann W AD - Department of Dermatology and Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. AD - Department of Dermatology, University of Luebeck, Luebeck, Germany. FAU - Rytlewski, Julie AU - Rytlewski J AUID- ORCID: 0000-0001-5244-6790 AD - Adaptive Biotechnologies, Seattle, WA, USA. FAU - Wilmott, James AU - Wilmott J AUID- ORCID: 0000-0002-6750-5244 AD - Melanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia. FAU - Mihm, Martin C Jr AU - Mihm MC Jr AD - Department of Dermatology and Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. FAU - Attrill, Grace H AU - Attrill GH AD - Melanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia. FAU - Dyring-Andersen, Beatrice AU - Dyring-Andersen B AD - Department of Dermatology and Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. AD - Novo Nordisk Foundation Centre for Protein Research, University of Copenhagen, Copenhagen, Denmark. FAU - Fields, Paul AU - Fields P AUID- ORCID: 0000-0002-9608-6464 AD - Adaptive Biotechnologies, Seattle, WA, USA. FAU - Zhan, Qian AU - Zhan Q AD - Department of Dermatology and Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. FAU - Colebatch, Andrew J AU - Colebatch AJ AD - Melanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia. AD - Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. FAU - Ferguson, Peter M AU - Ferguson PM AD - Melanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia. AD - Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. FAU - Thompson, John F AU - Thompson JF AUID- ORCID: 0000-0002-2816-2496 AD - Melanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia. AD - Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. FAU - Kallenbach, Klaus AU - Kallenbach K AD - Department of Surgical Pathology, Zealand University Hospital, Roskilde, Denmark. FAU - Yusko, Erik AU - Yusko E AD - Adaptive Biotechnologies, Seattle, WA, USA. FAU - Clark, Rachael A AU - Clark RA AD - Department of Dermatology and Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. FAU - Robins, Harlan AU - Robins H AD - Adaptive Biotechnologies, Seattle, WA, USA. AD - Fred Hutchinson Cancer Research Center, Seattle, WA, USA. FAU - Scolyer, Richard A AU - Scolyer RA AUID- ORCID: 0000-0002-8991-0013 AD - Melanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia. AD - Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. FAU - Kupper, Thomas S AU - Kupper TS AUID- ORCID: 0000-0002-4229-2916 AD - Department of Dermatology and Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. tkupper@bwh.harvard.edu. LA - eng GR - P30 CA006516/CA/NCI NIH HHS/United States GR - R01 AI127654/AI/NIAID NIH HHS/United States GR - R01 AR065807/AR/NIAMS NIH HHS/United States GR - R01 CA203721/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200120 PL - England TA - Nat Cancer JT - Nature cancer JID - 101761119 EIN - Nat Cancer. 2020 Apr;1(4):470. PMID: 35121971 MH - Humans MH - *Melanoma/genetics MH - T-Lymphocytes/pathology PMC - PMC7725220 MID - NIHMS1638625 EDAT- 2020/12/12 06:00 MHDA- 2020/12/12 06:01 PMCR- 2020/12/09 CRDT- 2020/12/11 06:06 PHST- 2020/12/11 06:06 [entrez] PHST- 2020/12/12 06:00 [pubmed] PHST- 2020/12/12 06:01 [medline] PHST- 2020/12/09 00:00 [pmc-release] AID - 10.1038/s43018-019-0019-5 [pii] AID - 10.1038/s43018-019-0019-5 [doi] PST - ppublish SO - Nat Cancer. 2020 Feb;1(2):197-209. doi: 10.1038/s43018-019-0019-5. Epub 2020 Jan 20.