NIMG-87. CHARACTERIZING IMMUNE PROFILES OF PEDIATRIC MEDULLOBLASTOMA AND THEIR RADIOLOGICAL CORRELATES. (14th November 2022)

• Record Type: Journal Article
• Authors: Familiar, Ariana; Zhao, Chao; Kim, Meen Chul; Khalili, Nastaran; Madhogarhia, Rachel; Arif, Sherjeel; Bagheri, Sina; Anderson, Hannah; Haldar, Debanjan; Ware, Jeffrey B; Vossough, Arastoo; Storm, Philip B; Resnick, Adam C; Kazerooni, Anahita Fathi; Nabavizadeh, Ali
• Is Part Of: Neuro-oncology. Volume 24(2022)Supplement 7
• Page Start: vii185
• Page End: vii185
• Publication Date: 2022-11-14
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noac209.705
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Recent studies have shown preliminary evidence for differentiation of the tumor microenvironment (TME) and immune landscape between molecularly-defined medulloblastoma (MB) subtypes. Identifying radiological correlates of these TME patterns could establish a non-invasive method of immune profile characterization for guiding patient-centered therapies. Here, we examine immune profiles between MB subtypes using data from Open Pediatric Brain Tumor Atlas (OpenPBTA), and their relationship to tumor measurements from pre-operative MRIs. We identified a retrospective cohort of 94 pediatric MB patients with available molecular subtyping and immune profiles (36 cell types) from bulk gene expression data. A random forest analysis was used to classify the four MB subtypes based on immune profiles. Four cell types had high impact on classification performance: plasmacytoid dendritic cells (PDC; 25.8% accuracy decrease when randomized), hematopoietic stem cells (HSC; 21.9%), plasma B cells (20.3%), and cancer associated fibroblasts (18.8%). Pairwise comparisons revealed SHH and WNT tumors had significantly higher numbers of fibroblasts and HSCs compared to Group3/Group4. We also found novel evidence for significantly lower amounts of plasma B cells in the SHH group, and high PDC levels in Group4, followed by Group3, and low PDC in SHH/WNT. Multi-parametric MRI scans for 39 patients were used to segment tumor volumes. Overall tumor volume was significantly correlated with composite stroma scores ( R = 0.34, p = 0.036). Additionally, patients with higher volumes of gadolinium contrast-enhancing compared to non-enhancing components had higher immune ( R = 0.42, p = 0.009) and microenvironment (summed immune and stromal cell types; R = 0.44, p = 0.006) scores, regardless of their molecular subtype. Together, our results demonstrate: (1) the use of rich immune profiles for differentiating molecular subtypes of MB and their unique TME characterization; and (2) initial evidence for radiological correlates of these profiles based on pre-operative imaging collected through standard practices.