瑞士日内瓦大学Mikal J. Pittet小组的论文发现了CCL3是由衰老的中性粒细胞在癌症中产生并促进肿瘤生长。相关论文于2026年2月5日发表于国际顶尖学术期刊《癌细胞》杂志上。

该研究团队引入了一种细胞类型概率分类器，可以从scRNAseq数据集中恢复低转录中性粒细胞，从而实现对TAN异质性的泛癌症分析。在190个人类和小鼠肿瘤中，该研究组发现了一个保守的分化轨迹，最终达到了终末期CCL3hi状态。这种状态表现出促肿瘤转录程序，包括那些参与缺氧适应和衰老的转录程序。一致地，CCL3hi TANs在人类和小鼠的缺氧肿瘤壁龛中富集。通过对小鼠中性粒细胞来源的CCL3的机制扰动，该研究团队发现它通过CCR1依赖的信号传导维持了缺氧肿瘤区域的TAN存活。这些发现证实了CCL3在肿瘤生长过程中是一种保守的标记物和促瘤中性粒细胞的功能驱动因子，并为解剖不同类型肿瘤的中性粒细胞生物学提供了一个可扩展的框架。

据介绍，肿瘤相关中性粒细胞（TANs）在癌症中丰富，但其表型多样性和功能状态仍不明确。

附：英文原文

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

Author: Evangelia Bolli, Pratyaksha Wirapati, Mehdi Hicham, Yuxuan Xie, Marie Siwicki, Florent Duval, Anne-Galle Goubet, Máté Kiss, Béatrice Zitti, Thomas Zwahlen, Sheri Mcdowell, Ruben Bill, Simona Angerani, Camilla Engblom, Seth Anderson, Aiping Jiang, Oliver Hartley, David B. Sykes, Maja Jankovic, Nadine Fournier, Matthias Gunzer, David Tarussio, Stéphanie Tissot, Peter M. Sadow, William C. Faquin, Moshe Sade-Feldman, Ralph Weissleder, Sara Pai, Franois Mercier, Robert Manguso, Mikal J. Pittet

Issue&Volume: 2026-02-05

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.

DOI: 10.1016/j.ccell.2026.01.006

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(26)00045-0