CCL3 is produced by aged neutrophils across cancers and promotes tumor growth.

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 CCL3hi state. This state exhibits pro-tumor transcriptional programs, including those involved in hypoxic adaptation and senescence. Consistently, CCL3hi 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.

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Publication Details

Journal
Open Access CRIS of the University of Bern
Published
2026-02-09
DOI
https://doi.org/10.48620/94527
Primary Topic
Immune cells in cancer
Type
article
Field-Weighted Citation Impact
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article

CCL3 is produced by aged neutrophils across cancers and promotes tumor growth.

Evangelia Bolli, Marie Siwicki, David Tarussio, Sheri A. C. McDowell et al.
Open Access CRIS of the University of Bern
Immune cells in cancer
article

CCL3 is produced by aged neutrophils across cancers and promotes tumor growth.

Evangelia Bolli, Marie Siwicki, David Tarussio, Sheri A. C. McDowell, Nadine Fournier, Mehdi Hicham, Sara I. Pai, Pratyaksha Wirapati, Simona Angerani, Sarah R. Philips, Béatrice Zitti, François Mercier, D. Sykes, Florent Duval, Moshe Sade-Feldman, Camilla Engblom, Ruben Bill, Seth Anderson, Peter M. Sadow, Aiping Jiang, Thomas Zwahlen, William C Faquin, Máté Kiss, Ralph Weissleder, Yuxuan Xie, Anne-Gaëlle Goubet, Maja Jankovic, Oliver Hartley, Stéphanie Tissot, Matthias Gunzer, Robert Manguso
article en

Abstract

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 CCL3hi state. This state exhibits pro-tumor transcriptional programs, including those involved in hypoxic adaptation and senescence. Consistently, CCL3hi 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.

Open Access CRIS of the University of Bern
Life in Land
Openalex Percentile: Top 60%
Immune cells in cancer
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