Virtual Flash Talk & E-Poster Presentation 34th Lorne Cancer Conference 2022

Uncovering subtype specific intra-tumoural heterogeneity in brain cancer (#9)

Saskia Freytag 1 2 , Jordan Jones 3 , Andrew Morokoff 3 , Samuel Roberts-Thomson 4 , Anna Pavenko 5 , Alison Vanschoiack 5 , Jim Whittle 1 2 6 , Sarah A Best 1 2
  1. Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Medical Biology, Melbourne University, Melbourne, Victoria, Australia
  3. Department of Surgery, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
  4. Department of Anatomical Pathology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  5. Technology Access Program, NanoString Technologies, Seattle, USA
  6. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

Brain cancer is a deadly disease with a treatment regime that remains unchanged for decades. In brain cancer biology, intra-tumoural heterogeneity (ITH) is fast becoming an essential element to understand the complex nature of solid tumours. With the advent of single cell sequencing, tumours that appear homogenous by pathology are revealing unforeseen heterogeneity in the tumour sample. Indeed, in high-grade glioma (i.e., glioblastoma, GBM), increased ITH is associated with more aggressive disease. The next step in investigating ITH is to spatially discern these clusters of transcriptionally distinct cell types to identify specific niches in which they reside and cells they associate with. In order to investigate spatial ITH of brain cancer, we have obtained surgical brain tumour samples from low-grade (IDH1-mutant) and high-grade (IDH1-wt) glioma patients. Though routine histological analysis of these samples indicates IDH1-mutant low-grade glioma are homogenous, we have evaluated spatial regions of interest with increased cycling cells (Ki67 staining) and immune infiltrate (CD45 staining) by spatial whole transcriptome analysis. This analysis suggests that there are deeper levels of heterogeneity in these samples than initially appreciated, likely involving cell-to-cell communication with spatial significance. Indeed, the mesenchymal-like IDH1-wt glioblastoma displayed immune infiltrate that was enriched with macrophages, unlike IDH1-mutant counterparts. Together, this primary study reveals increased ITH in high-grade glioma, and a diverse immune landscape between glioma subtypes, likely impacting response to immunotherapy treatments.