{
  "abstract": "Immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) in melanoma are influenced by the pre-treatment immune state. We investigated whether baseline autoantibodies directed against cytokines, chemokines, cytokine receptors, and immune-checkpoint/costimulatory proteins were associated with outcome in a regimen-dependent manner. Baseline sera from patients with metastatic melanoma were profiled on a multiplex bead array of 86 cytokine, chemokine, cytokine-receptor and immune-checkpoint antigens, and associations with best overall response and irAE development were assessed within pre-specified treatment strata by label-permutation testing with Benjamini–Hochberg false-discovery-rate control (SAM as a sensitivity analysis). Associations differed by ICI regimen. Anti-IL17A and anti-CCL2 reactivity was higher in patients developing irAEs under ipilimumab monotherapy (both p = 0.003) and shifted in the opposite direction under pembrolizumab without prior CTLA-4 therapy. Higher anti-PD-L1/CD274 and anti-CCL5 and lower anti-KIT reactivity were associated with response to pembrolizumab without prior CTLA-4 therapy (p = 0.025, p = 0.002, p = 0.006), and lower anti-MCAM and anti-CSF3 reactivity with response under ipilimumab/nivolumab (p = 0.001 and p = 0.002). No association survived false-discovery-rate correction, so all findings are exploratory and hypothesis-generating; higher baseline anti-IL10 reactivity was a leading irAE signal under pembrolizumab without prior CTLA-4 therapy (p = 0.027). These regimen-dependent humoral markers warrant prospective, regimen-stratified validation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Dermatology, University Hospital Heidelberg and National Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership Between DKFZ and University Hospital Heidelberg, 69120 Heidelberg, Germany",
    "German Cancer Consortium (DKTK), Core Center DKFZ Heidelberg, 69120 Heidelberg, Germany",
    "Medical Faculty, University Heidelberg, 69120 Heidelberg, Germany",
    "German Cancer Research Center (DKFZ), Applied Tumor Immunity, 69120 Heidelberg, Germany",
    "Alden Scientific Immune GmbH, 44227 Dortmund, Germany",
    "Department of Dermatology, University Hospital Zürich, 8091 Zürich, Switzerland",
    "Faculty of Medicine, University of Zürich, 8006 Zürich, Switzerland",
    "Department of Dermatology, University Hospital Zürich, University of Zürich, 8091 Zürich, Switzerland",
    "Department of Dermatology, Kantonsspital Aarau, 5001 Aarau, Switzerland",
    "Department of Dermatology, University Hospital Homburg/Saar, 66421 Homburg Saar, Germany",
    "Department of Dermatology, University Hospital Tübingen, 72076 Tübingen, Germany",
    "Skin Cancer Unit, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany",
    "Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, 68167 Mannheim, Germany",
    "DKFZ Hector Cancer Institute at the University Medical Center Mannheim, 68167 Mannheim, Germany",
    "Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany",
    "Skin Cancer Center at the University Cancer Center and National Center for Tumor Diseases Dresden, Department of Dermatology, University Hospital Carl Gustav Carus Dresden, 01307 Dresden, Germany"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Robin Reschke",
      "orcid": "0000-0002-2850-2526"
    },
    {
      "affs": [
        4
      ],
      "name": "Hans-Dieter Zucht"
    },
    {
      "affs": [
        4
      ],
      "name": "Petra Budde",
      "orcid": "0000-0001-8991-3495"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Joanna Mangana"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Reinhard Dummer",
      "orcid": "0000-0002-2279-6906"
    },
    {
      "affs": [
        9
      ],
      "name": "Claudia Pföhler",
      "orcid": "0000-0003-0384-114X"
    },
    {
      "affs": [
        10,
        11,
        12,
        13,
        14
      ],
      "name": "Kilian Wistuba-Hamprecht"
    },
    {
      "affs": [
        10
      ],
      "name": "Benjamin Weide"
    },
    {
      "affs": [
        15
      ],
      "name": "Friedegund Meier"
    },
    {
      "affs": [
        0
      ],
      "name": "Lara-Elena Hakim-Meibodi"
    },
    {
      "affs": [
        0
      ],
      "name": "Carsten Schulz"
    },
    {
      "affs": [
        0
      ],
      "name": "Jasmin Richter"
    },
    {
      "affs": [
        0
      ],
      "name": "Alexander H. Enk"
    },
    {
      "affs": [
        4
      ],
      "name": "Manuel Bräutigam"
    },
    {
      "affs": [
        4
      ],
      "name": "Thi Nhat Minh Nguyen"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jessica C. Hassel",
      "orcid": "0000-0001-7575-6230"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d59qeqg5nzj7q.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219746",
  "fulltext_url": null,
  "id": "d59qeqg5nzj7q",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9746",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/d59qeqg5nzj7q.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:54Z",
      "native_id": "10.3390/ijms27219746",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9746"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Regimen-Dependent Anti-Cytokine and Immune-Checkpoint Autoantibodies Are Associated with Immunotherapy Toxicity and Response in Melanoma",
  "title_text": "Regimen-Dependent Anti-Cytokine and Immune-Checkpoint Autoantibodies Are Associated with Immunotherapy Toxicity and Response in Melanoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T00:20:52Z",
  "url": "https://research.draconitic.com/paper/d59qeqg5nzj7q",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}