{
  "abstract": "Background: Reliable biomarkers for characterization of the risk of severe immune-related adverse events (irAEs) during immune checkpoint inhibition remain lacking. We hypothesized that early dynamics of complementary complete blood count (CBC)-based immune biomarkers may be associated with severe immune toxicity. We therefore evaluated longitudinal changes in absolute eosinophil count (AEC) and neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.\n\nMethods: This multicenter retrospective study included 503 patients with mRCC receiving nivolumab monotherapy in the second or later treatment line. Biomarker analyses were performed using a prespecified 28-day landmark design. AEC and NLR were evaluated at baseline, month 1, and as dynamic Low→High phenotypes, defined as transition from below the baseline upper-quartile threshold to the highest month-1 quartile. Multivariable logistic regression adjusted for age, sex, ECOG performance status, IMDC risk group, and treatment line.\n\nResults: Among 501 toxicity-evaluable patients, 57 (11.4%) developed grade 3–4 irAEs. Baseline AEC and NLR were not associated with severe irAEs. In contrast, the AEC Low→High phenotype was associated with severe irAEs after multivariable adjustment (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.02–4.97; P = 0.045), as was the NLR Low→High phenotype (aOR 2.77, 95% CI 1.25–6.17; P = 0.012). In a prespecified combined multivariable model, NLR remained independently associated with severe irAEs (aOR 2.81, 95% CI 1.25–6.30; P = 0.012), whereas the AEC association was attenuated (aOR 2.08, 95% CI 0.90–4.80; P = 0.085).\n\nConclusions: Early dynamics of eosinophils and NLR, rather than baseline biomarker values, were associated with severe irAEs during nivolumab therapy. These findings suggest that eosinophil expansion and inflammatory remodeling may reflect aspects of early immune activation associated with clinically significant immune toxicity. Longitudinal assessment of routinely available CBC-based immune biomarkers therefore warrants prospective validation in cohorts with time-resolved toxicity assessment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czechia",
    "Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia",
    "ARON Research Foundation ETS, Macerata, Italy",
    "Department of Oncology, University Hospital in Hradec Králové, Hradec Králové, Czechia",
    "Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czechia",
    "Department of Oncology, Second Faculty of Medicine, Charles University and Motol and Homolka University Hospital, Prague, Czechia",
    "Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czechia",
    "2 Department of Oncology, Faculty of Medicine, Comenius University, and National Cancer Institute, Bratislava, Slovakia",
    "Department of Radiotherapy and Oncology, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Košice, Slovakia",
    "Department of Oncology, F. D. Roosevelt University General Hospital, Banská Bystrica, Slovakia",
    "Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czechia",
    "Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czechia",
    "Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, Brno, Czechia",
    "Department of Urology, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czechia",
    "Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Bratislava, Slovakia"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ondřej Fiala"
    },
    {
      "affs": [
        0
      ],
      "name": "Jan Králíček"
    },
    {
      "affs": [
        3
      ],
      "name": "Jindřich Kopecký"
    },
    {
      "affs": [
        4
      ],
      "name": "Michal Vočka"
    },
    {
      "affs": [
        5
      ],
      "name": "Tomas Buchler"
    },
    {
      "affs": [
        6
      ],
      "name": "Hana Študentová"
    },
    {
      "affs": [
        7
      ],
      "name": "Jana Obertová"
    },
    {
      "affs": [
        7
      ],
      "name": "Beáta Rondzíková"
    },
    {
      "affs": [
        4
      ],
      "name": "Martin Matějů"
    },
    {
      "affs": [
        8
      ],
      "name": "Dominik Šafčák"
    },
    {
      "affs": [
        9
      ],
      "name": "Matej Hrnčár"
    },
    {
      "affs": [
        3
      ],
      "name": "Peter Priester"
    },
    {
      "affs": [
        6
      ],
      "name": "Martina Spisarová"
    },
    {
      "affs": [
        6
      ],
      "name": "Anežka Zemánková"
    },
    {
      "affs": [
        10
      ],
      "name": "Radka Lohynská"
    },
    {
      "affs": [
        0
      ],
      "name": "Michaela Tkadlecová"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Lucie Grmelová"
    },
    {
      "affs": [
        13
      ],
      "name": "Petr Stránský"
    },
    {
      "affs": [
        6
      ],
      "name": "Bohuslav Melichar"
    },
    {
      "affs": [
        7,
        14
      ],
      "name": "Patrik Palacka"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Alexandr Poprach"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/apfcxecc9dhpq.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1944728",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696394/",
  "id": "apfcxecc9dhpq",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://doi.org/10.3389/fimmu.2026.1944728",
  "language": "en",
  "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": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7221548711",
  "pdf_url": "https://europepmc.org/articles/PMC13696394?pdf=render",
  "pmcid": "PMC13696394",
  "pmid": "42935928",
  "published": "2026-10-12",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/apfcxecc9dhpq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:45Z",
      "native_id": "PMC13696394",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1944728"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1944728",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1944728/full"
    },
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42935928",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42935928"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Early dynamics of eosinophils and the neutrophil-to-lymphocyte ratio are associated with severe immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma",
  "title_text": "Early dynamics of eosinophils and the neutrophil-to-lymphocyte ratio are associated with severe immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:44Z",
  "url": "https://research.draconitic.com/paper/apfcxecc9dhpq",
  "venue": "Frontiers in Immunology",
  "versions": []
}