Epigenetic Priming Sensitizes Metastatic Breast Cancer to Checkpoint Blockade by Rewiring the Tumor-Immune Microenvironment.

Epigenetic priming with HDAC inhibitor and immune checkpoint blockade enhances anti-tumor response in metastatic breast cancer, achieving tumor eradication in models.

• Why it matters: Metastatic breast cancer often resists immune checkpoint therapies due to suppressive tumor microenvironment components, necessitating strategies to overcome this resistance.
• What they did: Gonzalez et al. combined single-cell transcriptomics, spatial proteomics, immunology, and mathematical modeling to study how entinostat with anti-PD-1/CTLA-4 sensitizes tumors, revealing multifaceted immune modulation.
• The result: The approach downregulates myeloid-mediated T-cell suppression and boosts B-cell activity, with models showing that targeting both T-cell activation and myeloid suppression is essential for tumor eradication, informing future treatments.