Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity.
Yura GrabovskaAlan MackayPatricia O'HareStephen CrosierMartina A FinettiEdward C SchwalbeJessica C PicklesAmy R FairchildAimee AveryJulia CockleRebecca HillJanet LindseyDebbie HicksMark KristiansenJane ChalkerJohn AndersonDarren R HargraveThomas S JacquesKarin StraathofSimon BaileyChris JonesSteven C CliffordDaniel WilliamsonPublished in: Nature communications (2020)
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.
Keyphrases
- high grade
- end stage renal disease
- chronic kidney disease
- blood brain barrier
- ejection fraction
- stem cells
- poor prognosis
- prognostic factors
- dna methylation
- genome wide
- risk assessment
- patient reported outcomes
- low grade
- bone marrow
- young adults
- cell therapy
- climate change
- mesenchymal stem cells
- current status
- childhood cancer