@article{bdfbdf69ab944c908f400e470f6236e7,
title = "Evaluating the impact of age on immune checkpoint therapy biomarkers",
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.",
keywords = "TCGA, aging, cancer, genomics, immune, immunotherapy",
author = "Rossin Erbe and Zheyu Wang and Sharon Wu and Joanne Xiu and Neeha Zaidi and Jennifer La and David Tuck and Nathanael Fillmore and Giraldo, {Nicolas A.} and Michael Topper and Stephen Baylin and Marc Lippman and Claudine Isaacs and Reva Basho and Ilya Serebriiskii and Lenz, {Heinz Josef} and Igor Astsaturov and John Marshall and Josephine Taverna and Jerry Lee and Jaffee, {Elizabeth M.} and {Roussos Torres}, {Evanthia T.} and Ashani Weeraratna and Hariharan Easwaran and Fertig, {Elana J.}",
note = "Funding Information: This work received funding from the National Cancer Institute P01CA247886-01A1 and P30CA006973-58 to E.J.F. the Lustgarten Foundation to E.J.F. the Grollman Glick Scholar award to H.E. and the National Institutes of Health U01AG066101 to H.E. The authors would like to thank Mara R. Lanis for her helpful discussions on TCR diversity and immune checkpoint genes. The results shown here are based upon data generated by the TCGA Research Network (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga), the METABRIC, the GENIE, CLS, and the GTEx Project (https://www.gtexportal.org/home/). The graphical abstract was created with BioRender. Conceptualization, R.E. N.Z. J. Lee, E.T.R.T. A.W. H.E. and E.J.F.; methodology, R.E. Z.W. S.W. J.X. J. La, D.T. N.F. N.A.G, and E.J.F.; software and formal analysis, R.E. Z.W. S.W. J. La, and N.A.G.; writing – original draft, R.E. H.E. and E.J.F.; writing – review & editing, R.E. Z.W. N.Z. M.T. M.L. C.I. R.B. I.S. H.-J.L. I.A. J.M. J.T. J. Lee, E.M.J. A.W. H.E. and E.J.F.; funding acquisition, E.M.J. S.B. H.E. and E.J.F.; visualization, R.E. and S.W.; supervision, H.E. and E.J.F. S.W. and J.X. are employees of Caris Life Sciences. E.J.F. is a consultant for Champions Oncology and is on the scientific advisory board for Viosera Therapeutics. Funding Information: This work received funding from the National Cancer Institute P01CA247886-01A1 and P30CA006973-58 to E.J.F., the Lustgarten Foundation to E.J.F., the Grollman Glick Scholar award to H.E., and the National Institutes of Health U01AG066101 to H.E. The authors would like to thank Mara R. Lanis for her helpful discussions on TCR diversity and immune checkpoint genes. The results shown here are based upon data generated by the TCGA Research Network ( https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga ), the METABRIC, the GENIE, CLS, and the GTEx Project ( https://www.gtexportal.org/home/ ). The graphical abstract was created with BioRender. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = aug,
day = "24",
doi = "10.1016/j.celrep.2021.109599",
language = "English (US)",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}