Nature Communications (Apr 2025)
Age-related divergence of circulating immune responses in patients with solid tumors treated with immune checkpoint inhibitors
- 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,
- Elsa Hallab,
- Madelena Brancati,
- Mari Nakazawa,
- Stephanie Alden,
- Christopher Thoburn,
- Nicole E. Gross,
- Alexei G. Hernandez,
- Erin M. Coyne,
- Emma Kartalia,
- Marina Baretti,
- Elizabeth M. Jaffee,
- Sanjay Bansal,
- Laura Tang,
- G. Scott Chandler,
- Rajat Mohindra,
- Won Jin Ho,
- Mark Yarchoan,
- Daniel J. Zabransky
Affiliations
- Chester Kao
- Department of Oncology, Johns Hopkins University School of Medicine
- Soren Charmsaz
- Department of Oncology, Johns Hopkins University School of Medicine
- Hua-Ling Tsai
- Department of Oncology, Johns Hopkins University School of Medicine
- Khaled Aziz
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine
- Daniel H. Shu
- Department of Oncology, Johns Hopkins University School of Medicine
- Kabeer Munjal
- Department of Oncology, Johns Hopkins University School of Medicine
- Ervin Griffin
- Department of Oncology, Johns Hopkins University School of Medicine
- James M. Leatherman
- Department of Oncology, Johns Hopkins University School of Medicine
- Evan J. Lipson
- Department of Oncology, Johns Hopkins University School of Medicine
- Yasser Ged
- Department of Oncology, Johns Hopkins University School of Medicine
- Jeannie Hoffman-Censits
- Department of Oncology, Johns Hopkins University School of Medicine
- Howard L. Li
- Department of Oncology, Johns Hopkins University School of Medicine
- Elsa Hallab
- Department of Oncology, Johns Hopkins University School of Medicine
- Madelena Brancati
- Department of Oncology, Johns Hopkins University School of Medicine
- Mari Nakazawa
- Department of Oncology, Johns Hopkins University School of Medicine
- Stephanie Alden
- Department of Oncology, Johns Hopkins University School of Medicine
- Christopher Thoburn
- Department of Oncology, Johns Hopkins University School of Medicine
- Nicole E. Gross
- Department of Oncology, Johns Hopkins University School of Medicine
- Alexei G. Hernandez
- Department of Oncology, Johns Hopkins University School of Medicine
- Erin M. Coyne
- Department of Oncology, Johns Hopkins University School of Medicine
- Emma Kartalia
- Department of Oncology, Johns Hopkins University School of Medicine
- Marina Baretti
- Department of Oncology, Johns Hopkins University School of Medicine
- Elizabeth M. Jaffee
- Department of Oncology, Johns Hopkins University School of Medicine
- Sanjay Bansal
- Genentech Inc, South San Francisco
- Laura Tang
- Genentech Inc, South San Francisco
- G. Scott Chandler
- F. Hoffmann-La Roche Ltd
- Rajat Mohindra
- F. Hoffmann-La Roche Ltd
- Won Jin Ho
- Department of Oncology, Johns Hopkins University School of Medicine
- Mark Yarchoan
- Department of Oncology, Johns Hopkins University School of Medicine
- Daniel J. Zabransky
- Department of Oncology, Johns Hopkins University School of Medicine
- DOI
- https://doi.org/10.1038/s41467-025-58512-z
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 16
Abstract
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.
