{
  "abstract": "Aging is accompanied by a progressive decline in immune function, increasing susceptibility to infections, cancer, and poorer treatment outcomes. The diversity of the T cell receptor (TCR) repertoire, reflecting the capacity to recognize diverse antigens, is known to decline with age. However, how intrinsic and extrinsic factors jointly shape TCR diversity and its rate of decline, as well as the extent to which this diversity influences clinical outcomes in cancer, remain poorly characterized. Here, we integrate TCR sequencing data from 1.32 billion unique T cell clones, derived from 798 patients with cancer and 5052 individuals without cancer across 14 independent cohorts, to systematically characterize the effects of age, sex, and chronic cytomegalovirus (CMV) infection on peripheral blood repertoire diversity. We identify a nonlinear trajectory of diversity loss that accelerates after midlife, with a marked increase in the rate of decline beyond approximately 50 years of age, which is further modified by sex and CMV infection. In patients with cancer, higher peripheral TCR diversity was associated with improved overall survival across multiple cancer types, even when accounting for the impact of age, sex, and CMV on diversity. Together, these findings underline peripheral TCR repertoire diversity as a dynamic marker of immune aging shaped by demographic and chronic viral factors.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Medicine (MOMA) Aarhus University Hospital Aarhus Denmark",
    "Department of Clinical Medicine Aarhus University Aarhus Denmark",
    "Department of Health Technology, Section for Bioinformatics Technical University of Denmark, DTU Lyngby Denmark",
    "Cancer Research UK Lung Cancer Centre of Excellence University College London Cancer Institute London UK",
    "Cancer Genome Evolution Research Group University College London Cancer Institute London UK",
    "Artificial Intelligence in Medicine (AIM) Program Mass General Brigham, Harvard Medical School Boston Massachusetts USA",
    "Department of Radiation Oncology Brigham and Women's Hospital and Dana‐Farber Cancer Institute, Harvard Medical School Boston Massachusetts USA",
    "Radiology and Nuclear Medicine GROW & CARIM, Maastricht University Maastricht the Netherlands"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Naja Lange",
      "orcid": "0009-0002-7406-3699"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Asbjørn K. Attermann",
      "orcid": "0009-0006-3307-0031"
    },
    {
      "affs": [
        0
      ],
      "name": "Randi Istrup Juul",
      "orcid": "0000-0001-7829-9071"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Laura Andersen",
      "orcid": "0009-0001-0223-3401"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Iver Nordentoft"
    },
    {
      "affs": [
        2
      ],
      "name": "Leon Eyrich Jessen",
      "orcid": "0000-0003-2879-2559"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Nicholas McGranahan",
      "orcid": "0000-0001-9537-4045"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "Hugo J. W. L. Aerts"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lars Dyrskjøt",
      "orcid": "0000-0001-7061-9851"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nicolai J. Birkbak",
      "orcid": "0000-0003-1613-9587"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9hnvpfv8grstg.bib",
  "cited_by": 0,
  "doi": "10.1111/acel.70777",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696440/",
  "id": "9hnvpfv8grstg",
  "issns": [
    "1474-9718",
    "1474-9726"
  ],
  "landing_url": "https://doi.org/10.1111/acel.70777",
  "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",
      "Research Article"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7223571013",
  "pdf_url": "https://europepmc.org/articles/PMC13696440?pdf=render",
  "pmcid": "PMC13696440",
  "pmid": "42928046",
  "published": "2026-10-25",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/9hnvpfv8grstg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:47Z",
      "native_id": "PMC13696440",
      "source": "pmc",
      "url": "https://doi.org/10.1111/acel.70777"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928046",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928046"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Nonlinear Aging of the Human TCR Repertoire Is Influenced by Sex, CMV, and Cancer",
  "title_text": "Nonlinear Aging of the Human TCR Repertoire Is Influenced by Sex, CMV, and Cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:46Z",
  "url": "https://research.draconitic.com/paper/9hnvpfv8grstg",
  "venue": "Aging Cell",
  "versions": []
}