Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity

Yura Grabovska, Alan Mackay, Patricia O’Hare, Stephen Crosier, Martina Finetti, Edward C. Schwalbe, Jessica C. Pickles, Amy R. Fairchild, Aimee Avery, Julia Cockle, Rebecca Hill, Janet Lindsey, Debbie Hicks, Mark Kristiansen, Jane Chalker, John Anderson, Darren Hargrave, Thomas S. Jacques, Karin Straathof, Simon BaileyChris Jones, Steven C. Clifford, Daniel Williamson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)
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Abstract

Immune-therapy is an attractive alternative therapeutic approach for targeting central nervous system (CNS) tumors and the constituency of the Tumor Immune Microenvironment (TIME) likely to predict patient response. Here, we describe the TIME of >6000 primarily pediatric CNS tumors using a deconvolution approach (methylCIBERSORT). We produce and validate a custom reference signature defining 11 non-cancer cell types to estimate relative proportions of infiltration in a panCNS tumor cohort spanning 80 subtypes. We group patients into three broad immune clusters associated with CNS tumor types/subtypes. In cohorts of medulloblastomas (n = 2325), malignant rhabdoid tumors (n = 229) and pediatric high-grade gliomas (n = 401), we show significant associations with molecular subgroups/subtypes, mutations, and prognosis. We further identify tumor-specific immune clusters with phenotypic characteristics relevant to immunotherapy response (i.e. Cytolytic score, PDL1 expression). Our analysis provides an indication of the potential future therapeutic and prognostic possibilities of immuno-methylomic profiling in pediatric CNS tumor patients that may ultimately inform approach to immune-therapy.

Original languageEnglish
Article number4324
Pages (from-to)4324
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020
Externally publishedYes

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