Bulk RNA sequencing of prostate cancer (PCa) primary tumors and metastases: Epworth Clinical Cohort

This progression is driven by an immunologically cold bone tumor microenvironment that fosters resistance to therapy. To define the mechanisms underlying this uniquely immunosuppressive niche, we applied spatial single cell analyses across primary tumors and metastatic sites.

Bone metastases showed marked suppression of tumor-intrinsic type I interferon (IFN-I) signaling and loss of antigen presentation, features that strongly predicted reduced bone metastasis-free survival. Tumor-intrinsic IFN-I expression correlated with memory T cell infiltration, whereas the bone myeloid compartment was enriched for protumor macrophages and showed reduced dendritic cell (DC) activation and antigen presentation.