IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58512-z.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58512-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-025-58512-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58512-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.