Clinically oriented immune heterogeneity in prostate cancer: emerging targets and strategies - PubMed
4 hours ago
- #immune heterogeneity
- #immunotherapy
- #prostate cancer
- Prostate cancer (PCa) is considered immunologically 'cold' with limited response to immune checkpoint inhibitors (ICIs).
- Single-cell and spatial profiling reveal immune heterogeneity in PCa, including immune-excluded glands, myeloid-suppressed stromal borders, and lymphocyte-rich niches with B-cell aggregates and tertiary lymphoid structures (TLS).
- TLS-high regions resemble inflamed, ICI-responsive cancers and may be targeted with biomarker-guided neoadjuvant or focal immunotherapy.
- Bone metastases are dominated by suppressive macrophage/monocyte programs and dysfunctional T cells, often driven by the CCL2-CCR6 axis.
- Standard therapies remodel immune ecosystems, creating inflammatory windows but fostering adaptive resistance.
- Myeloid-driven inflammation-coupled rewiring (e.g., IL-8/CXCR2 signaling, therapy-induced senescence/SASP) reinforces T-cell exclusion and exhaustion.
- Variable HLA class I loss and hypoxic/metabolic 'functional cold zones' contribute to immune evasion.
- A heterogeneity-aware framework integrates genomic responder subsets with microenvironmental stratification for tailored immunotherapy.
- Emerging strategies include T-cell redirection (PSMA/STEAP1 engagers, bispecifics, CAR-T) and myeloid-targeting combinations.