Age-related divergence of circulating immune responses in patients with solid tumors treated with immune checkpoint inhibitors
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.
Article Details
Authors (30)
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
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Howard L. Li
Johns Hopkins University School of Medicine, Baltimore
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