{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Transcriptome Analysis"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001007029"],"host":["EGA"],"description":["EGA study EGAS00001007029"],"dataset_title":["RNA sequencing of high-risk paediatric cancers for identifying T-cell infiltration signatures"],"repository":["EGA"],"category":["restricted"],"name_synonyms":["T-cell, primary cancer, Thymus-Dependent Lymphocytes, Malignant Neoplasm, Risk, Malignancy, T-Cells, Neoplasms, Thymus-Dependent, Risks, Benign Neoplasm, T, Benign Neoplasms, Lymphocytes, T-Lymphocyte, Cancers, T-lymphocyte, Tumor, Malignant, malignant tumor, Cell, Thymus-Dependent Lymphocyte, Neoplasias, Relative, T Cells, T cell, MT, Benign, T Lymphocyte, T-Cell, malignant neoplasm, mature T cell, Cells, Relative Risks, Neoplasm, T Cell, Malignancies, immature T cell, T Lymphocytes, T lymphocyte, Thymus Dependent Lymphocytes, Neoplasia, Lymphocyte, Relative Risk, Cancer, Tumors, Malignant Neoplasms."],"description_synonyms":["Ribonucleic, Biological Markers, Viral Marker, Materials, Surrogate Endpoints, T-cell surface antigen T4/Leu-3, determination, Laboratory, Feature, adult stage, Longterm., Biochemical, Endpoint, T-Lymphocyte, protein, Serum, Tumor, Technic, Long Term, Mutations, Relative, Laboratory Markers, Techniques, L3T4, Immunogold-Silver Techniques, T Lymphocyte, PDCD1L1, Biological, Method, Immunogold-Silver Technique, Ly-4, protein aggregate, Effect, B7-H1, immature T cell, Non Polyadenylated, adult, RNA Gene Products, Programmed death ligand 1, T-Cells, T, procedures, T Cells, Immune, Immunogold-Silver Technic, Markers, Methodological Studies, malignant neoplasm, Viral Markers, Immunolabeling Technique, Malignancies, Long-Term Effects, Immunogold Technics, Thymus Dependent Lymphocytes, PDL1, Tumors, DmelCG14283, Viral, Surrogate Endpoint, T-cell surface antigen T4|Leu-3, ribose nucleic acid, ribonucleic acids, Longterm Effect, Immunogold Technique, Genome Sequencing, Biochemical Markers, Procedure, Biologic Marker, results, Immunogold, Immunogold Techniques, Immunolabeling Technic, Complete Genome, Benign, PDCD1LG1, T-Cell, Marker, Ribonukleinsaeure, Algorithm, B7-H, Relative Risks, Immunolabeling Technics, pentosenucleic acids, Genetic Materials, Technics, Ribonucleic acids, Adults, Genetic Material, B7 homolog 1, Acid, T-cell, Immunotherapies, End Points, Risk, p32, T-cell surface glycoprotein CD4, Thymus-Dependent, common, Benign Neoplasms, Immunogold Silver Techniques, CD4mut, INSDC_feature:gene, Immunologic, Methodological, BcDNA:RH10246, Laboratory Marker, T-lymphocyte, Features, Methodological Study, Thymus-Dependent Lymphocyte, Malignant Neoplasms, T cell, Biochemical Marker, Material, Cells, Cistron, T Cell, Immunogold-Silver, Thymus-Dependent Lymphocytes, tmb, Procedures, Effects, Clinical Markers, Clinical Marker, Neoplasms, infiltrating, Benign Neoplasm, Gene, protein-containing complex, Malignant, Surrogate End Points, Surrogate Markers, Studies, Gene Products, MAL, Technique, Immunogold Silver Technics, CD274, Biomarker, Complete, Whole Genome, Clinical, Genetic, Malignancy, Longterm, Biological Marker, Complete Genome Sequencing, Long-Term, PD-L1, Sequencing, Non-Polyadenylated RNA, Study, Neoplasias, Immunologic Markers, Whole, mature T cell, Long-Term Effect, Characteristics, Immunologic Marker, T Lymphocytes, Biologic, Lymphocyte, Cancer, RNA, Malignant Neoplasm, Immunogold Technic, protein complex, Serum Markers, Proteins, Leu2, End Point, Immunohistocytochemistry, RNS, Cistrons, Cell, Immune Marker, Characteristic, MT, native protein, T-cell differentiation antigen L3T4, Surrogate End Point, yeast nucleic acid, Long Term Effects, Protein, chemical analysis, Neoplasm, PDCD1 ligand 1, background, techniques, T lymphocyte, Relative Risk, Biologic Markers, Immunolabeling, MRP-L55, B7H1, ribonucleic acid, Serum Marker, Immunocytochemistry, primary cancer, Surrogate, Non Polyadenylated RNA, Endpoints, Risks, Non-Polyadenylated, Lymphocytes, Ribonucleic Acid, Cancers, malignant tumor, Surrogate Marker, introduction, Longterm Effects, Protein Gene Products, Gene Proteins, Immunogold-Silver Technics, Immunolabeling Techniques, CG14283, CD4, assay, CD8, variable, Neoplasia, methodology, Immune Markers"],"additional_accession":[]},"is_claimable":false,"name":"A novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancer","description":"Background\nMolecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. We speculated that a more refined appreciation of the TIME in childhood cancers, rather than a reliance on commonly used biomarkers such as tumour mutation burden (TMB), neoantigen load and PD-L1 expression, is an essential prerequisite for improved immunotherapies in childhood solid cancers.\nMethods\nWe combined immunohistochemistry (IHC) with RNA-sequencing and whole genome sequencing across a diverse spectrum of high-risk paediatric cancers to develop an alternative, expression-based signature associated with CD8+ T-cell infiltration of the TIME. Further, we explored transcriptional features of immune archetypes, T-cell receptor sequencing diversity, assessed the relationship between CD8+ and CD4+ abundance by IHC and deconvolution predictions, and assessed common adult biomarkers such as neoantigen load and TMB.\nResults\nA novel 15-gene immune signature, Immune Paediatric Signature Score (IPASS), was identified. Using this signature, we estimate up to 31% of high-risk cancers harbour infiltrating T-cells. In addition, we showed that PD-L1 protein expression is poorly correlated with PD-L1 RNA expression and TMB and neoantigen load are not predictive of T-cell infiltration in paediatrics. Furthermore, deconvolution algorithms are only weakly correlated with IHC measurements of T-cells.\nConclusions\nOur data provides new insights into the variable immune-suppressive mechanisms dampening responses in paediatric solid cancers. Effective immune-based interventions in\nhigh-risk paediatric cancer will require individualised analysis of the TIME.","dates":{"updated":"2023-07-18 15:23:15"},"accession":"EGAS00001007029","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001010920","EGAC00001001869"]}}