Abstract
Little is known about the in vivo impacts of targeted therapy on melanoma cell abundance and protein expression. Here, 21 antibodies were added to an established melanoma mass cytometry panel to measure 32 cellular features, distinguish malignant cells, and characterize dabrafenib and trametinib responses in BRAF V600mut melanoma. Tumor cells were biopsied before neoadjuvant therapy and compared to cells surgically resected from the same site after 4 weeks of therapy. Approximately 50,000 cells per tumor were characterized by mass cytometry and computational tools t-SNE/viSNE, FlowSOM, and MEM. The resulting single-cell view of melanoma treatment response revealed initially heterogeneous melanoma tumors were consistently cleared of Nestin-expressing melanoma cells. Melanoma cell subsets that persisted to week 4 were heterogeneous but expressed SOX2 or SOX10 proteins and specifically lacked surface expression of MHC I proteins by MEM analysis. Traditional histology imaging of tissue microarrays from the same tumors confirmed mass cytometry results, including persistence of NES- SOX10+ S100β+ melanoma cells. This quantitative single-cell view of melanoma treatment response revealed protein features of malignant cells that are not eliminated by targeted therapy.
Original language | English (US) |
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Pages (from-to) | 708-719 |
Number of pages | 12 |
Journal | Pigment Cell and Melanoma Research |
Volume | 31 |
Issue number | 6 |
DOIs | |
State | Published - Nov 2018 |
Funding
Funding information J.M.I. is cofounder and board member at Cytobank Inc. and received research support from Incyte Corp and Janssen. This study was supported by NIH/NCI T32 CA009592 (D.B.D), R25 GM062459 (D.B.D), R25 CA136440 (K.E.D.), F31 CA199993 (A.R.G.), R00 CA143231 (J.M.I.), the Vanderbilt-Ingram Cancer Center (VICC, P30 CA68485), Vanderbilt Medical Scholars (J.S.G), and VICC Ambassadors. This study was supported by NIH/NCI T32 CA009592 (D.B.D), Cytobank Inc. and received research support from Incyte Corp and Janssen.
Keywords
- kinase inhibitors
- mass cytometry
- melanoma
- single cell
- targeted therapy
ASJC Scopus subject areas
- Oncology
- General Biochemistry, Genetics and Molecular Biology
- Dermatology