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000282687 1001_ $$aNabbi, Arash$$b0
000282687 245__ $$aTranscriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours.
000282687 260__ $$aLondon$$bBioMed Central$$c2023
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000282687 520__ $$aCancer immunotherapies including immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T-cell therapy have shown variable response rates in paediatric patients highlighting the need to establish robust biomarkers for patient selection. While the tumour microenvironment in adults has been widely studied to delineate determinants of immune response, the immune composition of paediatric solid tumours remains relatively uncharacterized calling for investigations to identify potential immune biomarkers.To inform immunotherapy approaches in paediatric cancers with embryonal origin, we performed an immunogenomic analysis of RNA-seq data from 925 treatment-naïve paediatric nervous system tumours (pedNST) spanning 12 cancer types from three publicly available data sets.Within pedNST, we uncovered four broad immune clusters: Paediatric Inflamed (10%), Myeloid Predominant (30%), Immune Neutral (43%) and Immune Desert (17%). We validated these clusters using immunohistochemistry, methylation immune inference and segmentation analysis of tissue images. We report shared biology of these immune clusters within and across cancer types, and characterization of specific immune cell frequencies as well as T- and B-cell repertoires. We found no associations between immune infiltration levels and tumour mutational burden, although molecular cancer entities were enriched within specific immune clusters.Given the heterogeneity of immune infiltration within pedNST, our findings suggest personalized immunogenomic profiling is needed to guide selection of immunotherapeutic strategies.
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000282687 650_7 $$2Other$$aCNS tumours
000282687 650_7 $$2Other$$aImmunogenomics
000282687 650_7 $$2Other$$aNeuroblastoma
000282687 650_7 $$2Other$$aPaediatric neuro-oncology
000282687 650_7 $$2Other$$aTumour microenvironment
000282687 7001_ $$0P:(DE-He78)b8f2b74d0482aed61472c7065dc1ed56$$aBeck, Pengbo$$b1$$eFirst author$$udkfz
000282687 7001_ $$aDelaidelli, Alberto$$b2
000282687 7001_ $$aOldridge, Derek A$$b3
000282687 7001_ $$aSudhaman, Sumedha$$b4
000282687 7001_ $$aZhu, Kelsey$$b5
000282687 7001_ $$aYang, S Y Cindy$$b6
000282687 7001_ $$aMulder, David T$$b7
000282687 7001_ $$aBruce, Jeffrey P$$b8
000282687 7001_ $$aPaulson, Joseph N$$b9
000282687 7001_ $$aRaman, Pichai$$b10
000282687 7001_ $$aZhu, Yuankun$$b11
000282687 7001_ $$aResnick, Adam C$$b12
000282687 7001_ $$aSorensen, Poul H$$b13
000282687 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b14$$udkfz
000282687 7001_ $$0P:(DE-He78)b0b3740107f746e09dc23fdf25eb0629$$aBrabetz, Sebastian$$b15
000282687 7001_ $$0P:(DE-He78)b84967c4f073b71405404f3719c788cd$$aLambo, Sander$$b16
000282687 7001_ $$aMalkin, David$$b17
000282687 7001_ $$0P:(DE-He78)3fdc3623477264cb5d0e14f256dbfbb8$$aJohann, Pascal$$b18$$udkfz
000282687 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b19$$udkfz
000282687 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b20$$udkfz
000282687 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b21$$udkfz
000282687 7001_ $$0P:(DE-He78)bff9e3e3d86865d2b0836bb8f3ce98f3$$aJäger, Natalie$$b22$$udkfz
000282687 7001_ $$00000-0002-8073-5888$$aPugh, Trevor J$$b23
000282687 773__ $$0PERI:(DE-600)2484394-5$$a10.1186/s13073-023-01219-x$$gVol. 15, no. 1, p. 67$$n1$$p67$$tGenome medicine$$v15$$x1756-994X$$y2023
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