Researchers have developed a novel single-cell RNA sequencing classifier to identify tumor-associated neutrophils (TANs), which are often missed by traditional data filters due to their low mRNA content. This tool revealed that high neutrophil abundance serves as a powerful independent predictor of poor cancer prognosis across various human malignancies. The study identifies a conserved three-state differentiation trajectory in both humans and mice, progressing from "young" cells to a terminally differentiated, pro-tumor state marked by CCL3 expression. Experimental evidence demonstrates that a CCL3-CCR1 signaling axis is essential for the survival of these neutrophils within hypoxic tumor regions. By sustaining themselves through this feedforward loop, CCL3-high neutrophils promote tumor growth, making them a significant potential target for future myeloid-targeted immunotherapies.

References:

• Bolli E, Wirapati P, Hicham M, et al. CCL3 is produced by aged neutrophils across cancers and promotes tumor growth[J]. Cancer Cell, 2026.