Evaluating the impact of age on immune checkpoint therapy biomarkers

Cell Reports

Joanne Xiu¹  Marc Lippman²  Zheyu Wang³  Jennifer La⁴  Neeha Zaidi⁴  Igor Astsaturov⁵  Reva Basho⁶  David Tuck⁶  Hariharan Easwaran⁶  Claudine Isaacs⁶  Sharon Wu⁶  Stephen Baylin⁶  Evanthia T. Roussos Torres⁷  Jerry Lee⁸  John Marshall⁸  Ashani Weeraratna⁹  Josephine Taverna⁹  Elana J. Fertig⁹  Elizabeth M. Jaffee^1,10  Ilya Serebriiskii^1,10  Heinz-Josef Lenz^1,10  Rossin Erbe^1,11  Nathanael Fillmore^1,12  Nicolas A. Giraldo^1,12  Michael Topper^1,12 

[1] Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA;Caris Life Sciences, Irving, TX, USA;Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Boulevard, AC-1046A, Los Angeles, CA 90048, USA;Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA;Division of Hematology and Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA;Fox Chase Cancer Center, Philadelphia, PA, USA;Keck School of Medicine, University of Southern California, Los Angeles, CA, USA;Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA;McKusick-Nathans Institute of the Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA;VA Boston Healthcare System, Boston, MA, USA;

关键词: cancer;    aging;    immune;    TCGA;    immunotherapy;    genomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown