Madawa Jayawardana

Supplementary Table S6 from Spatial Profiling Reveals Immune Escape Pathways and Therapeutic Vulnerabilities in Prostate Cancer Bone Metastases

Supplementary Table S7 from Spatial Profiling Reveals Immune Escape Pathways and Therapeutic Vulnerabilities in Prostate Cancer Bone Metastases

Macrophage phenotype and gene expression changes associate with bone metastasis

Prognostic value of IRF9, pSTAT1, and HLA-I expression in PCa progression

Prostate cancer frequently metastasizes to bone, marking incurable disease. 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 were strongly associated with 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 activation and antigen presentation. Digital spatial profiling of matched tumors revealed a broad loss of IFN-I-regulated immunostimulatory and checkpoint molecules. Notably, B7-H3, a putative negative regulator of IFN-I, was highly expressed in bone metastases and inversely associated with antigen presentation. These findings define bone-specific mechanisms of immune resistance and highlight therapeutic vulnerabilities that could inform precision therapeutic strategies for prostate cancer. Significance:Prostate cancer bone metastases establish a tumor-driven, immunosuppressive niche featuring global impairment of IFN-I signaling and antigen presentation coupled to elevated B7-H3, highlighting clinically actionable vulnerabilities in advanced prostate cancer.

Effector memory CTL infiltration associates with HLA-I/IRF9 status and metastasis risk

Prognostic significance of HLA-II expression and HLA-II+ DCs in PCa progression

Spatial profiling of tumor and stromal compartments in matched PCa bone metastases

B7-H3 is enriched in bone metastases and inversely associated with IRF9 and antigen presentation across human and PDX models of prostate cancer

Supplementary Table S3 from Spatial Profiling Reveals Immune Escape Pathways and Therapeutic Vulnerabilities in Prostate Cancer Bone Metastases