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 Bailey, Chris Jones, Steven C. Clifford and Daniel Williamson ()
Additional contact information
Yura Grabovska: Newcastle University
Alan Mackay: The Institute of Cancer Research
Patricia O’Hare: Great Ormond Street Hospital NHS Trust
Stephen Crosier: Newcastle University
Martina Finetti: Newcastle University
Edward C. Schwalbe: Newcastle University
Jessica C. Pickles: University College London Great Ormond Street Institute of Child Health
Amy R. Fairchild: University College London Great Ormond Street Institute of Child Health
Aimee Avery: Great Ormond Street Hospital for Children NHS Foundation Trust
Julia Cockle: The Institute of Cancer Research
Rebecca Hill: Newcastle University
Janet Lindsey: Newcastle University
Debbie Hicks: Newcastle University
Mark Kristiansen: UCL Great Ormond Street Institute of Child Health
Jane Chalker: Great Ormond Street Hospital for Children NHS Foundation Trust
John Anderson: Great Ormond Street Hospital NHS Trust
Darren Hargrave: Great Ormond Street Hospital NHS Trust
Thomas S. Jacques: Great Ormond Street Hospital for Children NHS Foundation Trust
Karin Straathof: Great Ormond Street Hospital NHS Trust
Simon Bailey: Newcastle University
Chris Jones: The Institute of Cancer Research
Steven C. Clifford: Newcastle University
Daniel Williamson: Newcastle University

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18070-y

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