Overview
- Researchers report that tumor-associated neutrophils adopt a terminal, aged CCL3hi state that promotes cancer growth through a CCL3–CCR1 signaling axis.
- Genetic mouse models lacking CCL3 in neutrophils or lacking neutrophil CCR1 showed impaired tumor support, demonstrating the functional importance of this pathway in vivo.
- These CCL3hi neutrophils preferentially occupy hypoxic tumor niches and activate gene programs that bolster their survival and enhance tumor progression.
- Neutrophils without CCL3 retain normal blood functions and still accumulate in tumors but no longer exhibit pro-tumor activity, indicating a specific role for CCL3 in their reprogramming.
- Published in Cancer Cell, the work proposes CCL3hi neutrophils as a cross-tumor prognostic biomarker and potential therapeutic target, complementing a 2023 macrophage-based variable and awaiting clinical validation.