{
  "abstract": "Background Although most studies of anticancer T-cell immunity focus on αβ T cells, γδ T cells are attracting increasing attention due to their involvement in antitumor immune responses in various cancer entities, including melanoma. While immune checkpoint blockade (ICB) using the antagonistic programmed cell death protein 1 (PD-1) antibodies nivolumab and pembrolizumab significantly improved the survival of patients with melanoma with distant metastasis, prognosis remains poor. PD-1 is not only expressed by αβ T cells but also by γδ T cells, making this numerically minor population of unconventional T cells, whose role in melanoma is still elusive, a target of ICB.Methods Here, we present a detailed γδ T-cell profiling study in late-stage melanoma at single-cell level using mass and polychromatic flow cytometry, T-cell receptor repertoire analyses and immunohistochemistry.Results Our analyses link high frequencies of peripheral Vδ1 T cells before the start of anti-PD-1 therapy to a significantly reduced overall survival. In these patients, the Vδ1 compartment is dominated by a late-differentiated senescent-like phenotype that is presumably unresponsive to therapy. This phenotype is less prevalent at the tumor site and analysis of RNA sequencing data revealed that the abundance of Vδ1 T cells within the tumor was positively associated with survival.Conclusions Our study suggests that Vδ1 T cells are associated with clinical outcomes, with a responsive subset expanding under ICB in patients where such a response remains possible. The observed clinical effects may be supported by the infiltration of these cells into the tumor, where they contribute to cancer immunosurveillance.",
  "authors": [
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany",
        "Section for Clinical Bioinformatics, Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany",
        "M3 Research Center, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Nicola Herold"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany",
        "Section for Clinical Bioinformatics, Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany",
        "M3 Research Center, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Jonas Bochem"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Johanna Leyens"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Svenja Wingerter"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Stephan Forchhammer"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany",
        "Section for Clinical Bioinformatics, Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany",
        "M3 Research Center, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Janine Spreuer"
    },
    {
      "affiliations": [
        "Institut of Immunology, Medizinische Hochschule Hannover, Hannover, Germany"
      ],
      "name": "Malte Deseke"
    },
    {
      "affiliations": [
        "Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Can Yurttas"
    },
    {
      "affiliations": [
        "Systems Cancer Immunology, Comprehensive Cancer Centre, King’s College London, London, Germany"
      ],
      "name": "Paola Nocerino"
    },
    {
      "affiliations": [
        "Systems Cancer Immunology, Comprehensive Cancer Centre, King’s College London, London, Germany"
      ],
      "name": "Rita Antunes dos Reis"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Teresa Amaral"
    },
    {
      "affiliations": [
        "Department of Dermatology, Venereology and Allergology, Kantonsspital St. Gallen, St. Gallen, Switzerland"
      ],
      "name": "Nikolaus B Wagner"
    },
    {
      "affiliations": [
        "Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Karolin Thiel"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Daniel Soffel"
    },
    {
      "affiliations": [
        "Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Kristin Bieber"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Schleswig-Holstein Lübeck Campus, Lübeck, Germany"
      ],
      "name": "Patrick Terheyden"
    },
    {
      "affiliations": [
        "Institute of Immunology, University Medical Center Schleswig-Holstein, Campus Kiel, Christian-Albrechts University, Kiel, Germany"
      ],
      "name": "Daniela Wesch"
    },
    {
      "affiliations": [
        "Institute of Immunology, University Medical Center Schleswig-Holstein, Campus Kiel, Christian-Albrechts University, Kiel, Germany"
      ],
      "name": "Hans-Heinrich Oberg"
    },
    {
      "affiliations": [
        "Institute for Experimental Cancer Research, Kiel University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany"
      ],
      "name": "Susanne Sebens"
    },
    {
      "affiliations": [
        "Section for Clinical Bioinformatics, Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany",
        "M3 Research Center, University Hospital Tübingen, Tübingen, Germany",
        "Department of Computer Science, University of Tübingen, Tübingen, Germany",
        "Institute for Bioinformatics and Medical Informatics, University of Tübingen, Tübingen, Germany",
        "Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany"
      ],
      "name": "Manfred Claassen"
    },
    {
      "affiliations": [
        "Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany",
        "Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany"
      ],
      "name": "Alfred Königsrainer"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Claus Garbe"
    },
    {
      "affiliations": [
        "Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany",
        "Health Sciences North Research Institute, Sudbury, Ontario, Canada"
      ],
      "name": "Graham Pawelec"
    },
    {
      "affiliations": [
        "Department of Dermatology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany",
        "Skin Cancer Center at the University Cancer Center Dresden and National Center for Tumor Diseases, Dresden, Germany"
      ],
      "name": "Friedegund Meier"
    },
    {
      "affiliations": [
        "Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany",
        "Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany",
        "Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany",
        "Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Markus W Löffler"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Benjamin Weide"
    },
    {
      "affiliations": [
        "Institut of Immunology, Medizinische Hochschule Hannover, Hannover, Germany",
        "Institute of Systems Immunology, Hamburg Center for Translational Immunology (HCTI), Hamburg, Germany"
      ],
      "name": "Immo Prinz"
    },
    {
      "affiliations": [
        "Institut of Immunology, Medizinische Hochschule Hannover, Hannover, Germany"
      ],
      "name": "Sarina Ravens"
    },
    {
      "affiliations": [
        "Systems Cancer Immunology, Comprehensive Cancer Centre, King’s College London, London, Germany",
        "Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy",
        "Haematology Department, Guy's Hospital, London, UK"
      ],
      "name": "Shahram Kordasti"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany",
        "Department of Dermatology, Venereology, and Allergology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin",
        "Berlin, Berlin, Germany"
      ],
      "name": "Thomas Eigentler"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Tübingen, Tübingen, Germany",
        "Section for Clinical Bioinformatics, Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany",
        "M3 Research Center, University Hospital Tübingen, Tübingen, Germany",
        "Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany",
        "Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany",
        "Skin Cancer Unit, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany",
        "Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany"
      ],
      "name": "Kilian Wistuba-Hamprecht"
    }
  ],
  "title": "Vδ1 T-cell subset appears to be responsive to PD-1 blockade therapy and is associated with survival in melanoma",
  "uid": "2eb57293-a3e8-5e2d-8a84-5375fe1641c0"
}