南京大学李颜小组宣布他们的最新研究揭示了人髓细胞和偏髓细胞期中性粒细胞抑制肿瘤免疫并促进癌症进展。该项研究成果发表在2025年7月15日出版的《细胞研究》上。

小组将人类和小鼠中性粒细胞分为三个发育阶段，包括早幼粒细胞（PM）、髓细胞和变髓细胞（MC和MM）和带状和节段性中性粒细胞（BD和SC）。基于这种分离，小组观察到骨髓（BM）中人类而非小鼠MC和MM期中性粒细胞的优势，它们具有强大的免疫抑制和促肿瘤特性。在17种癌症类型的患者中，MCs和MMs也占据了TINs的大部分。

此外，通过NOD/ShiLtJGpt-Prkdc^em26Cd52Il2rg^em26Cd22/Gpt (NCG)-Gfi1^-/-人类免疫系统（HIS）小鼠模型，支持人类TIN的有效重组，该课题组人员发现荷瘤小鼠中BM MCs和MM显著增加。通过比较BM和肿瘤中人类中性粒细胞的单细胞RNA测序分析结果，该研究团队发现CD63和Galectin-3可以区分MC和MM与癌症患者的中性粒细胞群体。

此外，该课题组提出了一种利用Fms样酪氨酸激酶3配体特异性诱导MCs和MMs向单核细胞的反分化的策略，并在NCG-Gfi1-/-HIS小鼠中触发肿瘤控制。因此，他们的发现确立了人类MC和MM期中性粒细胞在促进癌症进展中的重要作用，并表明它们有潜力成为开发潜在生物标志物和癌症免疫疗法的靶点。

研究人员表示，肿瘤浸润中性粒细胞（TINs）是高度异质性的，在肿瘤免疫微环境（TIME）中大多具有免疫抑制作用。目前的TIN生物标志物和针对TIN的治疗策略尚未在各种癌症类型的患者中产生最佳反应。

附：英文原文

Title: Human myelocyte and metamyelocyte-stage neutrophils suppress tumor immunity and promote cancer progression

Author: Liu, Wei, Shi, Tao, Lu, Chun, Che, Keying, Zhang, Zijian, Luo, Yuting, Hirschhorn, Daniel, Wang, Hanbing, Liu, Shaorui, Wang, Yan, Liu, Shuang, Sun, Haiqiao, Lu, Jun, Liu, Yuan, Shi, Dongquan, Ding, Shuai, Xu, Heping, Lu, Liaoxun, Xu, Jianming, Xin, Jun, Liang, Yinming, Merghoub, Taha, Wei, Jia, Li, Yan

Issue&Volume: 2025-07-15

Abstract: Tumor-infiltrating neutrophils (TINs) are highly heterogeneous and mostly immunosuppressive in the tumor immune microenvironment (TIME). Current biomarkers of TINs and treatment strategies targeting TINs have not yielded optimal responses in patients across cancer types. Here, we separated human and mouse neutrophils into three developmental stages, including promyelocyte (PM), myelocyte & metamyelocyte (MC & MM), and band & segmented (BD & SC) neutrophils. Based on this separation, we observed the predominance of human but not mouse MC & MM-stage neutrophils in bone marrow (BM), which exhibit potent immunosuppressive and tumor-promoting properties. MCs & MMs also occupy the majority of TINs among patients with 17 cancer types. Moreover, through the creation of a NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG)-Gfi1/ human immune system (HIS) mouse model, which supports efficient reconstitution of human TIN, we found a significant increase of BM MCs & MMs in tumor-bearing mice. By comparing the single-cell RNA sequencing analysis results of human neutrophils from both BM and tumors, we found that CD63 and Galectin-3 distinguish MC & MM from neutrophil populations in cancer patients. Furthermore, we proposed a strategy with Fms-like tyrosine kinase 3 ligand to specifically induce the trans-differentiation of MCs & MMs into monocytic cells, and trigger tumor control in NCG-Gfi1/ HIS mice. Thus, our findings establish an essential role of human MC & MM-stage neutrophils in promoting cancer progression, and suggest their potential as targets for developing potential biomarkers and immunotherapies for cancer.

DOI: 10.1038/s41422-025-01145-0

Source: https://www.nature.com/articles/s41422-025-01145-0