Ewing sarcoma survival splits by neighborhood, not mutation: a 135-patient spatial map yields four prognostic types, with interferon-reactive tumors faring best
Ewing sarcoma is genomically near-uniform yet patients fare very differently. Single-cell and spatial transcriptomics of tumors and their microenvironment in 135 patients identified five tumor-cell transcriptional states and eight niches defined by neighboring cell configurations, and niche composition sorted patients into Fusion Active, Proliferative, Immune Reactive and TME-enriched types. The Immune Reactive type, marked by interferon-activated tumor cells, had favorable survival, and the survival differences reproduced in two independent bulk transcriptomic cohorts.