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While adult tumour microenvironments are well characterized, the immune composition of paediatric solid tumours remains insufficiently mapped. This study performs an immunogenomic analysis of RNA-seq from 925 treatment-naïve paediatric nervous system tumours across 12 cancer types and defines immune cluster patterns linked to immune-cell frequencies and B- and T-cell repertoires.",{"@graph":69,"@context":121},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/transcriptional-immunogenomic-analysis-reveals-distinct-immunological-clusters-in-paediatric-nervous-system-tumours/386249/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/transcriptional-immunogenomic-analysis-reveals-distinct-immunological-clusters-in-paediatric-nervous-system-tumours/386249.png","ImageObject",300,407,{"name":92,"@type":93},"Chumphorn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":101,"interactionType":102,"userInteractionCount":4},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What is the main goal of the immunogenomic analysis in this study?","Question",{"text":111,"@type":112},"To identify potential immune biomarkers for paediatric immunotherapy decision-making by characterizing the immune composition of paediatric nervous system tumours using RNA-seq–based immunogenomic analysis.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"How many immune clusters were identified within paediatric nervous system tumours?",{"text":116,"@type":112},"Four broad immune clusters were uncovered: Paediatric Inflamed (10%), Myeloid Predominant (30%), Immune Neutral (43%), and Immune Desert (17%).",{"name":118,"@type":109,"acceptedAnswer":119},"Did the study find a link between immune infiltration and tumour mutational burden?",{"text":120,"@type":112},"No. The study reports no associations between immune infiltration levels and tumour mutational burden, while molecular cancer entities were enriched within specific immune clusters.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},386249,1790272922,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":4,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":128,"read_time":26},2336475401981,"https://ap-avatar.wpscdn.com/avatar/22000c94efd8d5204d?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786935347598174694","Nabbi etal. Genome Medicine (2023) 15:67 [https://doi.org/10.1186/s13073-023-01219-x](https://doi.org/10.1186/s13073-023-01219-x)  \nGenome Medicine  \n RESEARCH Open Access  \nTranscriptional immunogenomic analysis reveals distinct immunological clusters  \nin paediatric nervous system tumours  \nArash Nabbi1†, Pengbo Beck2,3†, Alberto Delaidelli4,5, Derek A. Oldridge6,7, Sumedha Sudhaman8, Kelsey Zhu1, S. Y. Cindy Yang1, David T. Mulder 1, Jeffrey P. Bruce 1, Joseph N. Paulson9, Pichai Raman 10, Yuankun Zhu10, Adam C. Resnick 10, Poul H. Sorensen4,5, Martin Sill2,3, Sebastian Brabetz2,3, Sander Lambo2,3, David Malkin8, Pascal D. Johann2,3,11, Marcel Kool2,3,12, David T. W. Jones2,13, Stefan M. Pfister2,3,11, Natalie Jäger2,3* and Trevor J. Pugh 1,14,15*  \nAbstract  \nBackground Cancer 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.  \nMethods 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.  \nResults 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 asTand 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.  \nConclusions Given the heterogeneity of immune infiltration within pedNST, our findings suggest personalized immunogenomic profiling is needed to guide selection of immunotherapeutic strategies.  \nKeywords Paediatric neuro-oncology, Immunogenomics, CNS tumours, Tumour microenvironment, Neuroblastoma  \n†Arash Nabbi and Pengbo Beck contributed equally to this work.  \n*Correspondence:  \nNatalie Jäger  \nn.jaeger@kitz-heidelberg.de Trevor J. Pugh [trevor.pugh@utoronto.ca](trevor.pugh@utoronto.ca)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[http://creativeco](http://creativeco)[mmons.org/publicdomain/zero/1.0/](","cbCaipqyexwLMiTR","https://ap.wps.com/l/cbCaipqyexwLMiTR","pdf",6590446,24,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Background\n## Rationale for biomarkers\n## Immunogenomic analysis and prior biomarkers","[{\"question\":\"What is the main goal of the immunogenomic analysis in this study?\",\"answer\":\"To identify potential immune biomarkers for paediatric immunotherapy decision-making by characterizing the immune composition of paediatric nervous system tumours using RNA-seq–based immunogenomic analysis.\"},{\"question\":\"How many immune clusters were identified within paediatric nervous system tumours?\",\"answer\":\"Four broad immune clusters were uncovered: Paediatric Inflamed (10%), Myeloid Predominant (30%), Immune Neutral (43%), and Immune Desert (17%).\"},{\"question\":\"Did the study find a link between immune infiltration and tumour mutational burden?\",\"answer\":\"No. The study reports no associations between immune infiltration levels and tumour mutational burden, while molecular cancer entities were enriched within specific immune clusters.\"}]","Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours | PDF"]