Therapy-resistance in AT/RT is driven by epithelial-mesenchymal transition, extracellular matrix changes, and enrichment of CD1A+ CD207+ dendritic cells [RNA-seq_cell_lines]

The TME of AT/RT recurrences was characterized by enrichment of CD1A+ CD207+ dendritic cells (DCs), which were per se associated with inferior survival in relapsed patients. Differentially expressed genes of AT/RT-MYC primary tumor cells that potentially persist after therapy, were involved in the organization of the extracellular matrix (ECM), developmental processes, and diverse immune signalling pathways. In addition, recurrences demonstrated a significantly higher proportion of cells undergoing partial epithelial-mesenchymal transition (pEMT) compared to primary tumors, a feature that we confirmed following treating AT/RT-MYC tumor cells in vitro.

Finally, patients with primary tumors strongly expressing respective genes displayed a significantly worse survival. We identified pEMT, ECM remodeling, and enrichment of CD1A+ CD207+ DCs as potential mechanisms of therapy resistance in AT/RT which could be employed to improve therapy in the future.