Overview
- The Sylvester Comprehensive Cancer Center team published the findings in Science Translational Medicine on Nov. 5, 2025.
- ER+ tumor cells producing DLL1 recruit PD‑L1+ CD163+ tumor‑associated macrophages via a CCR3/CCL7 axis that maintains cancer stem cells and drives CD8 T‑cell exhaustion.
- Blocking DLL1 and PD‑L1 together with low‑dose tamoxifen reduced tumor growth, depleted cancer stem cells, and reprogrammed the immunosuppressive tumor microenvironment in mouse models and patient‑derived explants.
- Tumors with high DLL1 and abundant PD‑L1+ macrophages correlated with resistance to tamoxifen and fulvestrant and with poorer survival in assessed samples, suggesting a potential biomarker for high‑risk patients.
- The authors caution that the approach remains preclinical and call for extended in vivo studies and pilot clinical trials, noting that immunotherapy has not yet been proven in luminal ER+ breast cancer.