| First Author | Bolli E | Year | 2026 |
| Journal | Cancer Cell | Volume | 44 |
| Issue | 3 | Pages | 624-640.e12 |
| PubMed ID | 41650972 | Mgi Jnum | J:392325 |
| Mgi Id | MGI:8319553 | Doi | 10.1016/j.ccell.2026.01.006 |
| Citation | Bolli E, et al. (2026) CCL3 is produced by aged neutrophils across cancers and promotes tumor growth. Cancer Cell 44(3):624-640.e12 |
| abstractText | Tumor-associated neutrophils (TANs) are abundant across cancers, yet their phenotypic diversity and functional states remain poorly defined. Here, we introduce a cell-type probability classifier that recovers low-transcript neutrophils from scRNAseq datasets, enabling pan-cancer analyses of TAN heterogeneity. Across >190 human and murine tumors, we identify a conserved differentiation trajectory that culminates in a terminal CCL3(hi) state. This state exhibits pro-tumor transcriptional programs, including those involved in hypoxic adaptation and senescence. Consistently, CCL3(hi) TANs are enriched in hypoxic tumor niches in both humans and mice. Through mechanistic perturbations of neutrophil-derived CCL3 in mice, we show that it sustains TAN survival in hypoxic tumor regions via CCR1-dependent signaling. These findings establish CCL3 as a conserved marker and functional driver of pro-tumor neutrophils in growing tumors, and provide a scalable framework for dissecting neutrophil biology across cancer types. |
