CCR4+low-density neutrophils define a novel immunosuppressive subset associated with breast cancer progression and early mortality
Neutrophils are increasingly recognized as key players in cancer progression, yet their functional heterogeneity limits their therapeutic exploitation. In breast cancer (BC), elevated circulating and tumor-associated neutrophils have been associated with poor prognosis, and low-density neutrophils (LDN), particularly, have been linked to immunosuppression. However, the specific neutrophil subsets…
Neutrophils, once thought to solely fuel cancer progression, now appear to harbor a hidden subset that may be key to suppressing the immune system and promoting tumor growth. In breast cancer (BC), higher levels of low-density neutrophils (LDN), particularly those expressing CCR4, have been linked to worse outcomes. This novel CCR4+LDN subset, abundant in late-stage disease, correlates with accelerated progression and reduced survival.
Serial blood samples reveal these cells fluctuate over time, with increases signaling near-term risk for metastatic patients. The CCR4+LDN subset is immunosuppressive, migrating more readily to tumor sites and hindering T cell-mediated tumor destruction, even when PD-1 blockade is employed. In a small study of Triple-Negative BC patients receiving anti-PD-1 therapy, early changes in this population were tied to treatment response.
These findings identify a distinct neutrophil population actively involved in immune evasion and tumor progression, making CCR4+LDN a minimally invasive real-time biomarker for disease course and treatment response, and suggesting a promising target for neutrophil-focused therapies in BC.
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