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Age-related divergence of circulating immune responses in patients with solid tumors treated with immune checkpoint inhibitors

Author

Listed:
  • Chester Kao

    (Johns Hopkins University School of Medicine)

  • Soren Charmsaz

    (Johns Hopkins University School of Medicine)

  • Hua-Ling Tsai

    (Johns Hopkins University School of Medicine)

  • Khaled Aziz

    (Johns Hopkins University School of Medicine)

  • Daniel H. Shu

    (Johns Hopkins University School of Medicine)

  • Kabeer Munjal

    (Johns Hopkins University School of Medicine)

  • Ervin Griffin

    (Johns Hopkins University School of Medicine)

  • James M. Leatherman

    (Johns Hopkins University School of Medicine)

  • Evan J. Lipson

    (Johns Hopkins University School of Medicine)

  • Yasser Ged

    (Johns Hopkins University School of Medicine)

  • Jeannie Hoffman-Censits

    (Johns Hopkins University School of Medicine)

  • Howard L. Li

    (Johns Hopkins University School of Medicine)

  • Elsa Hallab

    (Johns Hopkins University School of Medicine)

  • Madelena Brancati

    (Johns Hopkins University School of Medicine)

  • Mari Nakazawa

    (Johns Hopkins University School of Medicine)

  • Stephanie Alden

    (Johns Hopkins University School of Medicine)

  • Christopher Thoburn

    (Johns Hopkins University School of Medicine)

  • Nicole E. Gross

    (Johns Hopkins University School of Medicine)

  • Alexei G. Hernandez

    (Johns Hopkins University School of Medicine)

  • Erin M. Coyne

    (Johns Hopkins University School of Medicine)

  • Emma Kartalia

    (Johns Hopkins University School of Medicine)

  • Marina Baretti

    (Johns Hopkins University School of Medicine)

  • Elizabeth M. Jaffee

    (Johns Hopkins University School of Medicine
    Johns Hopkins University)

  • Sanjay Bansal

    (South San Francisco)

  • Laura Tang

    (South San Francisco)

  • G. Scott Chandler

    (F. Hoffmann-La Roche Ltd)

  • Rajat Mohindra

    (F. Hoffmann-La Roche Ltd)

  • Won Jin Ho

    (Johns Hopkins University School of Medicine
    Johns Hopkins University)

  • Mark Yarchoan

    (Johns Hopkins University School of Medicine
    Johns Hopkins University)

  • Daniel J. Zabransky

    (Johns Hopkins University School of Medicine
    Johns Hopkins University)

Abstract

Most new cancer diagnoses occur in patients over the age of 65. The composition and function of the immune system changes with age, but how the aged immune system affects responses to immune checkpoint inhibitor (ICI) cancer therapies remains incompletely understood. Here, using multiplex cytokine assay and high-parameter mass cytometry, we analyze prospectively collected blood samples from 104 cancer patients receiving ICIs. We find aged patients ( ≥ 65-years-old; n = 54) derive similar clinical outcomes as younger patients (n = 50). However, aged, compared to young, patients have divergent immune phenotypes at baseline that persist during ICI therapy, including diminished cytokine responses, reduced pools of naïve T cells with increased relative expression of immune checkpoint molecules, and more robust effector T cell expansion in responders compared to non-responders. Our study provides insights into age-stratified mechanisms of ICI effects while also implying the utility of age-tailored immunotherapeutic approaches.

Suggested Citation

  • Chester Kao & Soren Charmsaz & Hua-Ling Tsai & Khaled Aziz & Daniel H. Shu & Kabeer Munjal & Ervin Griffin & James M. Leatherman & Evan J. Lipson & Yasser Ged & Jeannie Hoffman-Censits & Howard L. Li , 2025. "Age-related divergence of circulating immune responses in patients with solid tumors treated with immune checkpoint inhibitors," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58512-z
    DOI: 10.1038/s41467-025-58512-z
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