biostudies-literatureDeMartino JEuropean Research Council3074https://www.ebi.ac.uk/biostudies/studies/S-EPMC10224926biostudies-literatureUnknown14(1)Paediatric rhabdomyosarcoma (RMS) is a soft tissue malignancy of mesenchymal origin that is thought to arise as a consequence of derailed myogenic differentiation. Despite intensive treatment regimens, the prognosis for high-risk patients remains dismal. The cellular differentiation states underlying RMS and how these relate to patient outcomes remain largely elusive. Here, we use single-cell mRNA sequencing to generate a transcriptomic atlas of RMS. Analysis of the RMS tumour niche reveals evidence of an immunosuppressive microenvironment. We also identify a putative interaction between NECTIN3 and TIGIT, specific to the more aggressive fusion-positive (FP) RMS subtype, as a potential cause of tumour-induced T-cell dysfunction. In malignant RMS cells, we define transcriptional programs reNature communicationsSingle-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma.PMC10224926850571Brok MVisser LLDeMartino JHolstege FCPHiemcke-Jiwa LSWezenaar AKLDrost JMargaritis Tde Souza TRios ACMeister MTGroot Koerkamp MJAMerks JHMfalseSingle-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma.Paediatric rhabdomyosarcoma (RMS) is a soft tissue malignancy of mesenchymal origin that is thought to arise as a consequence of derailed myogenic differentiation. Despite intensive treatment regimens, the prognosis for high-risk patients remains dismal. The cellular differentiation states underlying RMS and how these relate to patient outcomes remain largely elusive. Here, we use single-cell mRNA sequencing to generate a transcriptomic atlas of RMS. Analysis of the RMS tumour niche reveals evidence of an immunosuppressive microenvironment. We also identify a putative interaction between NECTIN3 and TIGIT, specific to the more aggressive fusion-positive (FP) RMS subtype, as a potential cause of tumour-induced T-cell dysfunction. In malignant RMS cells, we define transcriptional programs re2023-01-01T00:00:00Z2023 May2026-05-29T00:03:13.483Z2025-04-07T05:08:25.504ZS-EPMC102249263724491210.1038/s41467-023-38886-8