Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence

Margaret Johnson, April Bell, Kristen L. Lauing, Erik Ladomersky, Lijie Zhai, Manon Penco-Campillo, Yajas Shah, Elizabeth Mauer, Joanne Xiu, Theodore Nicolaides, Michael Drumm, Kathleen McCortney, Olivier Elemento, Miri Kim, Prashant Bommi, Justin T. Low, Ruba Memon, Jennifer Wu, Junfei Zhao, Xinlei MiMichael J. Glantz, Soma Sengupta, Brandyn Castro, Bakhtiar Yamini, Craig Horbinski, Darren J. Baker, Theresa L. Walunas, Gary E. Schiltz, Rimas V. Lukas, Derek A. Wainwright

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Purpose: Glioblastoma (GBM) is the most common aggressive mice with or without a brain tumor. The survival of young and old primary malignant brain tumor in adults with a median age of onset wild-type or transgenic (INK-ATTAC) mice with a brain tumor was of 68 to 70 years old. Although advanced age is often associated with evaluated after treatment with or without senolytics and/or poorer GBM patient survival, the predominant source(s) of malimmunotherapy. adaptive aging effects remains to be established. Here, we studied Results: Human patients with GBM ≥65 years of age had a ntratumoral and extratumoral relationships between adult patients significantly decreased survival compared with their younger with GBM and mice with brain tumors across the lifespan. counterparts. While the intra-GBM molecular profiles were simExperimental Design: Electronic health records at Northwestern ilar between younger and older patients with GBM, non-tumor Medicine and the NCI SEER databases were evaluated for GBM brain tissue had a significantly different gene expression profile patient age and overall survival. The commercial Tempus and Caris between young and old mice with a brain tumor and the eradidatabases, as well as The Cancer Genome Atlas were profiled for cation of senescent cells improved immunotherapy-dependent gene expression, DNA methylation, and mutational changes with survival of old but not young mice. varying GBM patient age. In addition, gene expression analysis was Conclusions: This work suggests a potential benefit for com-performed on the extratumoral brain of younger and older adult bining senolytics with immunotherapy in older patients with GBM.

Original languageEnglish (US)
Pages (from-to)4973-4989
Number of pages17
JournalClinical Cancer Research
Volume29
Issue number23
DOIs
StatePublished - 2023

All Science Journal Classification (ASJC) codes

  • General Medicine

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