title: Establishing High Dimensional Immune Signatures from Peripheral Blood via Mass Cytometry in a Discovery Cohort of Stage IV Melanoma Patients.
abstract: The identification of blood-borne biomarkers correlating with melanoma patient survival remains elusive. Novel techniques such as mass cytometry could help to identify melanoma biomarkers, allowing simultaneous detection of up to 100 parameters. However, the evaluation of multiparametric data generated via time-of-flight mass cytometry requires novel analytical techniques because the application of conventional gating strategies currently used in polychromatic flow cytometry is not feasible. In this study, we have employed 38-channel time-of-flight mass cytometry analysis to generate comprehensive immune cell signatures using matrix boolean analysis in a cohort of 28 stage IV melanoma patients and 17 controls. Clusters of parameters were constructed from the abundance of cellular phenotypes significantly different between patients and controls. This approach identified patient-specific combinatorial immune signatures consisting of high-resolution subsets of the T cell, NK cell, B cell, and myeloid compartments. An association with superior survival was characterized by a balanced distribution of myeloid-derived suppressor cell-like and APC-like myeloid phenotypes and differentiated NK cells. The results of this study in a discovery cohort of melanoma patients suggest that multifactorial immune signatures have the potential to allow more accurate prediction of individual patient outcome. Further investigation of the identified immune signatures in a validation cohort is now warranted.
authors.affiliation: Department of Internal Medicine II, University Medical Center, 72072 Tübingen, Germany.|Department of Dermatology, University Medical Center, 72076 Tübingen, Germany.
authors.forename: Kilian
authors.initials: K
authors.lastname: Wistuba-Hamprecht
authors.affiliation: Department of Internal Medicine II, University Medical Center, 72072 Tübingen, Germany.|Department of Dermatology, University Medical Center, 72076 Tübingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Martens
authors.affiliation: Department of Dermatology, University Medical Center, 72076 Tübingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weide
authors.affiliation: Singapore Immunology Network, Biopolis, Agency for Science, Technology and Research, 138648 Singapore.
authors.forename: Karen Wei Weng
authors.identifier: 0000-0001-5180-4429
authors.initials: KW
authors.lastname: Teng
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Zelba
authors.affiliation: Department of Dermatology, University Medical Center, 72076 Tübingen, Germany.
authors.forename: Elena
authors.identifier: 0000-0003-2809-3459
authors.initials: E
authors.lastname: Guffart
authors.affiliation: Singapore Immunology Network, Biopolis, Agency for Science, Technology and Research, 138648 Singapore.
authors.forename: Jinmiao
authors.identifier: 0000-0001-7547-6423
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Dermatology, University Medical Center, 72076 Tübingen, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.affiliation: Singapore Immunology Network, Biopolis, Agency for Science, Technology and Research, 138648 Singapore; graham.pawelec@uni-tuebingen.de Evan_Newell@immunol.a-star.edu.sg Anis_Larbi@immunol.a-star.edu.sg.
authors.forename: Evan William
authors.identifier: 0000-0002-2889-243X
authors.initials: EW
authors.lastname: Newell
authors.affiliation: Singapore Immunology Network, Biopolis, Agency for Science, Technology and Research, 138648 Singapore; graham.pawelec@uni-tuebingen.de Evan_Newell@immunol.a-star.edu.sg Anis_Larbi@immunol.a-star.edu.sg.
authors.forename: Anis
authors.initials: A
authors.lastname: Larbi
authors.affiliation: Department of Internal Medicine II, University Medical Center, 72072 Tübingen, Germany; graham.pawelec@uni-tuebingen.de Evan_Newell@immunol.a-star.edu.sg Anis_Larbi@immunol.a-star.edu.sg.|John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, United Kingdom; and.|Division of Cancer Studies, Faculty of Life Sciences and Medicine, King's College London, London SE5 9NU, United Kingdom.
authors.forename: Graham
authors.identifier: 0000-0002-3600-0163
authors.initials: G
authors.lastname: Pawelec
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D016000:Cluster Analysis; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor