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Erbe R , Wang Z , Wu S , Xiu J , Zaidi N , La J , Tuck D , Fillmore N , Giraldo NA , Topper M , Baylin S , Lippman M , Isaacs C , Basho R , Serebriiskii I , Lenz HJ , Astsaturov I , Marshall J , Taverna J , Lee J , Jaffee EM , Roussos Torres ET , Weeraratna A , Easwaran H , Fertig EJ
Evaluating the impact of age on immune checkpoint therapy biomarkers
Cell Rep. 2021 Aug 24;36(8) :109599
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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.
Notes
2211-1247 Erbe, Rossin Wang, Zheyu Wu, Sharon Xiu, Joanne Zaidi, Neeha La, Jennifer Tuck, David Fillmore, Nathanael Giraldo, Nicolas A Topper, Michael Baylin, Stephen Lippman, Marc Isaacs, Claudine Basho, Reva Serebriiskii, Ilya Lenz, Heinz-Josef Astsaturov, Igor Marshall, John Taverna, Josephine Lee, Jerry Jaffee, Elizabeth M Roussos Torres, Evanthia T Weeraratna, Ashani Easwaran, Hariharan Fertig, Elana J Journal Article United States Cell Rep. 2021 Aug 24;36(8):109599. doi: 10.1016/j.celrep.2021.109599.