Proteomic landscapes of Ewing sarcoma unravel immunological regulation of tumor progression

To gain a comprehensive molecular and functional view of the tumors in their microenvironment, we performed a deep mass spectrometry-based proteomic analysis of 168 tumors from 72 patients from primary, relapsed, and metastatic tumors. Analysis of more than 10,000 proteins across patients revealed novel insights into cancer prognosis, chemo-resistance, and progression. We found ferroptosis inhibition as a potential mediator of EWS chemo-resistance and identified novel subclasses of EWS that link the tumor immune landscape with DNA damage repair, ubiquitin-related proteins, and patient prognosis. Validation by multiplexed immunofluorescence imaging confirmed a significant association between patient prognosis and tumor neutrophils, suggesting potential neutrophil-targeted strategies for future treatment