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 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 J. Thoburn, Nicole Groß, Alexei Hernandez, Erin M. Coyne, Emma Kartalia, Marina Baretti, Elizabeth M. Jaffee, SB Bansal, Laura Tang, G. Scott Chandler, Rajat Mohindra, Won Jin Ho, Mark Yarchoan, Daniel J. Zabransky
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.