Cell Reports (Aug 2021)
Evaluating the impact of age on immune checkpoint therapy biomarkers
- Rossin Erbe,
- Zheyu Wang,
- Sharon Wu,
- Joanne Xiu,
- Neeha Zaidi,
- Jennifer La,
- David Tuck,
- Nathanael Fillmore,
- Nicolas A. Giraldo,
- Michael Topper,
- Stephen Baylin,
- Marc Lippman,
- Claudine Isaacs,
- Reva Basho,
- Ilya Serebriiskii,
- Heinz-Josef Lenz,
- Igor Astsaturov,
- John Marshall,
- Josephine Taverna,
- Jerry Lee,
- Elizabeth M. Jaffee,
- Evanthia T. Roussos Torres,
- Ashani Weeraratna,
- Hariharan Easwaran,
- Elana J. Fertig
Affiliations
- Rossin Erbe
- McKusick-Nathans Institute of the Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Zheyu Wang
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Sharon Wu
- Caris Life Sciences, Irving, TX, USA
- Joanne Xiu
- Caris Life Sciences, Irving, TX, USA
- Neeha Zaidi
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Jennifer La
- VA Boston Healthcare System, Boston, MA, USA
- David Tuck
- VA Boston Healthcare System, Boston, MA, USA
- Nathanael Fillmore
- VA Boston Healthcare System, Boston, MA, USA
- Nicolas A. Giraldo
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Michael Topper
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Stephen Baylin
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Marc Lippman
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA
- Claudine Isaacs
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA
- Reva Basho
- Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Boulevard, #AC-1046A, Los Angeles, CA 90048, USA
- Ilya Serebriiskii
- Fox Chase Cancer Center, Philadelphia, PA, USA
- Heinz-Josef Lenz
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Igor Astsaturov
- Fox Chase Cancer Center, Philadelphia, PA, USA
- John Marshall
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA
- Josephine Taverna
- Division of Hematology and Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
- Jerry Lee
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Elizabeth M. Jaffee
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Evanthia T. Roussos Torres
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Ashani Weeraratna
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Hariharan Easwaran
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Elana J. Fertig
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Applied Mathematics and Statistics, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins Bloomberg School of Medicine, Baltimore, MD, USA; Corresponding author
- Journal volume & issue
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Vol. 36,
no. 8
p. 109599
Abstract
Summary: Both tumors and aging alter the immune landscape of tissues. These interactions may play an important role in tumor progression among elderly patients and may suggest considerations for patient care. We leverage large-scale genomic and clinical databases to perform comprehensive comparative analysis of molecular and cellular markers of immune checkpoint blockade (ICB) response with patient age. These analyses demonstrate that aging is associated with increased tumor mutational burden, increased expression and decreased promoter methylation of immune checkpoint genes, and increased interferon gamma signaling in older patients in many cancer types studied, all of which are expected to promote ICB efficacy. Concurrently, we observe age-related alterations that might be expected to reduce ICB efficacy, such as decreases in T cell receptor diversity. Altogether, these changes suggest the capacity for robust ICB response in many older patients, which may warrant large-scale prospective study on ICB therapies among patients of advanced age.
