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 LeeElizabeth M. Jaffee, Evanthia T. Roussos Torres, Ashani Weeraratna, Hariharan Easwaran, Elana J. Fertig

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number109599
JournalCell Reports
Volume36
Issue number8
DOIs
StatePublished - Aug 24 2021

Keywords

  • TCGA
  • aging
  • cancer
  • genomics
  • immune
  • immunotherapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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