Age-related divergence of circulating immune responses in patients with solid tumors treated with immune checkpoint inhibitors
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.
Authors
- Soren Charmsaz (ORCID: https://orcid.org/0000-0002-9148-9870)
- Daniel J. Zabransky (ORCID: https://orcid.org/0000-0002-8184-3346)
- Alexei Hernandez (ORCID: https://orcid.org/0000-0002-6044-2631)
- Emma Kartalia (ORCID: https://orcid.org/0009-0000-6891-0498)
- Kabeer Munjal (ORCID: https://orcid.org/0009-0008-4151-635X)
- Rajat Mohindra (ORCID: https://orcid.org/0009-0000-4233-5210)
- Evan J. Lipson (ORCID: https://orcid.org/0000-0003-2976-0911)
- Mari Nakazawa (ORCID: https://orcid.org/0000-0001-6055-8960)
- Daniel Shu
- Marina Baretti (ORCID: https://orcid.org/0000-0003-0125-2405)
- Christopher J. Thoburn (ORCID: https://orcid.org/0000-0001-7743-9183)
- Madelena Brancati (ORCID: https://orcid.org/0009-0009-2401-3694)
- Chester Kao (ORCID: https://orcid.org/0000-0003-2568-2071)
- Erin M. Coyne (ORCID: https://orcid.org/0000-0002-0393-6600)
- Stephanie Alden (ORCID: https://orcid.org/0000-0003-0500-8696)
- Hua‐Ling Tsai (ORCID: https://orcid.org/0000-0001-8388-6297)
- Won Jin Ho (ORCID: https://orcid.org/0000-0003-2644-5086)
- Nicole Groß (ORCID: https://orcid.org/0000-0002-8936-207X)
- Elizabeth M. Jaffee (ORCID: https://orcid.org/0000-0003-3841-6549)
- Howard Liu Li (ORCID: https://orcid.org/0000-0003-2223-5444)
- Yasser Ged (ORCID: https://orcid.org/0000-0001-6671-7002)
- James M. Leatherman (ORCID: https://orcid.org/0000-0002-1721-2128)
- Mark Yarchoan (ORCID: https://orcid.org/0000-0003-4401-0748)
- G. Scott Chandler (ORCID: https://orcid.org/0000-0001-5339-9906)
- Jeannie Hoffman-Censits
- Ervin Griffin
- Elsa Hallab (ORCID: https://orcid.org/0000-0002-5322-8901)
- Laura Tang (ORCID: https://orcid.org/0000-0002-8013-3529)
- Khaled Aziz
- Sanjay Bansal
Institutions
- Roche (Switzerland) (CH)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Convergence (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-21
- DOI
- https://doi.org/10.1038/s41467-025-58512-z
- Citations
- 23
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 24.04
Funders
- Johns Hopkins University
- Swim Across America
- National Institutes of Health
- Genentech
- University of Texas MD Anderson Cancer Center
- National Cancer Institute
- Moonshot Research and Development Program
- Cancer Moonshot