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

Chester Kao(Johns Hopkins University), Soren Charmsaz(Johns Hopkins University), Hua‐Ling Tsai(Johns Hopkins University), Khaled Aziz(Johns Hopkins University), Daniel Shu(Johns Hopkins University), Kabeer Munjal(Johns Hopkins University), Ervin Griffin(Johns Hopkins University), James M. Leatherman(Johns Hopkins University), Evan J. Lipson(Johns Hopkins University), Yasser Ged(Johns Hopkins University), Jeannie Hoffman-Censits(Johns Hopkins University), Howard L. Li(Johns Hopkins University), Elsa Hallab(Johns Hopkins University), Madelena Brancati(Johns Hopkins University), Mari Nakazawa(Johns Hopkins University), Stephanie Alden(Johns Hopkins University), Christopher J. Thoburn(Johns Hopkins University), Nicole Groß(Johns Hopkins University), Alexei Hernandez(Johns Hopkins University), Erin M. Coyne(Johns Hopkins University), Emma Kartalia(Johns Hopkins University), Marina Baretti(Johns Hopkins University), Elizabeth M. Jaffee(Johns Hopkins University), SB Bansal, Laura Tang, G. Scott Chandler(Roche (Switzerland)), Rajat Mohindra(Roche (Switzerland)), Won Jin Ho(Johns Hopkins University), Mark Yarchoan(Johns Hopkins University), Daniel J. Zabransky(Johns Hopkins University)
Nature Communications
April 21, 2025
10.1038/s41467-025-58512-z
Cited by 25Open Access
Full Text

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.

Related Papers

No related papers found

Powered by citation graph analysis