Spatial Profiling Reveals Immune Escape Pathways and Therapeutic Vulnerabilities in Prostate Cancer Bone Metastases.

Bone metastases from prostate cancer show suppressed tumor-intrinsic type I interferon signaling and antigen presentation, linked to reduced bone metastasis-free survival, with B7-H3 highly expressed.

• Why it matters: Bone metastases create an immunologically cold microenvironment that resists therapy, but the spatial mechanisms of this immune escape are not well defined.
• What they did: Spatial single-cell analyses across primary and metastatic sites assessed IFN-I signaling, antigen presentation, and immune-cell states, including digital spatial profiling of matched tumors.
• The result: Bone myeloid compartments were enriched for protumor macrophages with reduced dendritic cell activation, and B7-H3 expression inversely associated with antigen presentation, suggesting bone-specific therapeutic vulnerabilities.

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