Abstract LB024: Cancer stem cells are enriched in human recurrent glioblastoma

Abstract

Abstract A number of studies have described an essential role of cancer stem cells (CSC) in glioblastoma (GBM) progression and recurrence based on isolation by candidate markers. However, a systematic evaluation of the proposed CSC in paired human primary and recurrent glioblastoma has been lacking and whether they represent a unified cell type with conserved features over tumor evolution is unresolved. In this study, we used human patient derived xenografts (PDX) to investigate the status of these cells in patients following therapeutics and recurrence. Firstly, to ensure the fidelity of tumor heterogeneity in serially passaged orthotopic GBM PDX, we collected samples at different passages and performed whole tumor single cell RNA sequencing analysis. The results illustrate the preservation of all unsupervised transcriptional cell clusters through multiple passages. Furthermore, treatment of tumor bearing mice with temozolomide, the standard of care chemotherapeutic drug for glioblastoma patients, increased apoptosis and decreased tumor cell burden but spared CSC. We then turned to paired human primary and recurrent GBM samples to inquire cancer stem cell marker expression and cell distribution. In all three pairs of PDX studied, cancer stem cell marker F3 serves as a reliable means to isolate sphere formation cells and is augmented in the recurrent samples. Inspection of whole tumors with single cell RNA sequencing nails down the enrichment of CSC in recurrent tumors, thus emphasizing the importance to eradicate these cells in future therapeutics. Citation Format: Xuanhua Peter Xie, Mungunsarnai Ganbold, Alicia Pedraza, Luis Parada. Cancer stem cells are enriched in human recurrent glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB024.