Desmoplastic small round cell tumors (DSRCT) are rare, incurable, male-predominant abdominal tumors associated with a 20% 5-year patient survival rate. Though all malignant cells harbor a pathognomonic EWSR1::WT1 fusion protein (FP), FP antagonists don’t yet exist. Importantly, DSRCT presents with desmoplastic stroma containing cancer-associated fibroblasts (CAFs) and extracellular matrix, a hallmark of this disease. Although much of the focus has been on the malignant small round cells, the role of the TME has yet to be explored. Given this context, we seek to understand the role of tumor-stroma interactions and the spatial heterogeneity within DSRCT to reveal potential therapeutic vulnerabilities. We created a 20-panel marker developed to interrogate the cellular constituents of the TME and to characterize the multilineage expression DSRCT. Cells were annotated using protein markers to identify blood vessels, fibroblasts, myeloid cells, and tumor cells. The tumor cells were further segregated based on androgen receptor (AR) expression. Among AR-positive tumor nests, AR localized primarily to the nucleus, suggesting downstream activation of this pathway. High AR expression also correlated with positive expression of pan-cytokeratin in the tumor nests and negative correlation to neuroendocrine markers.This work lays the foundation for spatial analysis of DSRCT. Future aims will include antibody panels specific to different cells of the TME, such as CAFs or immune cells. While there is no drug that targets the FP, we envision that understanding the tumor-stroma crosstalk may present a therapeutic opportunity.
