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Previous classification was based on histology, alveolar RMS (ARMS) or embryonal RMS (ERMS). In other paediatric cancers, fusion gene status has been shown to associate with differences in the tumour microenvironment (TME). However, comprehensive understanding of the TME in RMS and how it may differ between subtypes is lacking. This systematic review aimed to identify differences in the TME between fusion-positive RMS and fusion-negative RMS, to better understand how the fusion gene drives malignancy. The Web of Science, MEDLINE (Ovid), and EMBASE (Ovid) were searched to identify relevant studies investigating the TME in RMS. A total of 17 studies met the inclusion criteria and were included in the review, but only three studies specified fusion status in their sample data. Nine studies investigated the extracellular matrix and stroma, and another nine investigated the immune microenvironment. Significant differences in CD163+ macrophages, matrix metalloproteinases and stromal platelet-derived growth factor receptors-\u03b1\/\u03b2 were observed between ARMS and ERMS. Regarding fusion status, there were differences in the prevalence of T cell dysfunction, NECTIN-3 expression, and genes related to PD-1 signalling and interferon (IFN) response. This review highlights a need for further research of the TME in each fusion subtype. This will improve our understanding of how the fusion gene drives malignancy and ultimately aids in the development of novel treatment strategies.<\/jats:p>","DOI":"10.1093\/carcin\/bgag011","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:54:50Z","timestamp":1771505690000},"source":"Crossref","is-referenced-by-count":1,"title":["The tumour microenvironment in paediatric rhabdomyosarcomas: a systematic review"],"prefix":"10.1093","volume":"47","author":[{"given":"Megan","family":"Richards","sequence":"first","affiliation":[{"name":"School of Cancer Sciences, Faculty of Medicine, University of Southampton , Southampton SO17 1BJ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Putnam","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, Faculty of Medicine, University of Southampton , Southampton SO17 1BJ ,","place":["United 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