BRAF and MEK inhibitor therapy eliminates Nestin-expressing melanoma cells in human tumors

Pigment Cell & Melanoma Research
Deon B DoxieJonathan M Irish

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 BRAFV600mut 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 ...Continue Reading

References

Apr 22, 2003·Journal of Cellular Physiology·Angel Garcia-LoraFederico Garrido
Jun 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Giao Q PhanSteven A Rosenberg
Sep 25, 2003·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Peter O Krutzik, Garry P Nolan
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Jun 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jonathan M IrishRonald Levy
Jun 26, 2010·Current Protocols in Cytometry·Nikesh KotechaJonathan M Irish
Oct 22, 2010·Stem Cells·Donghyun ParkBruce T Lahn
Mar 9, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nikhil WagleLevi A Garraway
Apr 26, 2012·International Journal of Cancer. Journal International Du Cancer·Friederike ErdmannFreddie Bray
Jul 24, 2012·Cell·Eran HodisLynda Chin
Jan 12, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dennie T FrederickJennifer A Wargo
Feb 19, 2013·Oncology Reports·Michiko AkiyamaSeiji Kawana
Mar 29, 2013·Nature Reviews. Cancer·Michael HölzelThomas Tüting
Jun 4, 2013·The New England Journal of Medicine·Omid HamidAntoni Ribas
Sep 4, 2013·Current Opinion in Immunology·Zach B BjornsonWendy J Fantl
Sep 14, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Rita G LadsteinLars A Akslen
Sep 21, 2013·Nature·Corbin E Meacham, Sean J Morrison
Nov 23, 2013·Cancer Discovery·Eliezer M Van AllenUNKNOWN Dermatologic Cooperative Oncology Group of Germany (DeCOG)
Mar 26, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gary L JohnsonLee M Graves
Jun 14, 2014·Science·Anoop P PatelBradley E Bernstein
Jul 22, 2014·Nature·Bing ZhangUNKNOWN NCI CPTAC
Nov 5, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Chung-Wei LeeGeorge F Murphy
Nov 15, 2014·Nature Immunology·Jonathan Michael Irish
Nov 20, 2014·Nature·David Holmes
Jan 8, 2015·Development·Marcos Simões-Costa, Marianne E Bronner
Jan 13, 2015·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Sofie Van GassenYvan Saeys
May 17, 2015·Methods : a Companion to Methods in Enzymology·Kirsten E DigginsJonathan M Irish
Jul 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hannah G PolikowskyJonathan M Irish
Nov 7, 2015·Methods in Molecular Biology·Nalin LeelatianJonathan M Irish
Nov 26, 2015·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Katherine J NicholasSpyros A Kalams
May 8, 2016·Cell·Matthew H Spitzer, Garry P Nolan
Sep 7, 2016·Cytometry. Part B, Clinical Cytometry·Nalin LeelatianJonathan M Irish
Oct 13, 2016·Cell Metabolism·Yue J WangKlaus H Kaestner
Nov 3, 2016·The New England Journal of Medicine·Douglas B JohnsonJavid J Moslehi
Jan 31, 2017·Nature Methods·Kirsten E DigginsJonathan M Irish

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Citations

Dec 15, 2018·The FEBS Journal·Akshitkumar M MistryJonathan M Irish
Nov 21, 2019·Expert Review of Molecular Diagnostics·Sara CarpiPaola Nieri
Jul 1, 2020·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Timothy J KeyesKara L Davis
Nov 11, 2018·Cancer Immunology Research·Allison R GreenplateJonathan M Irish

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