荷兰癌症研究所Karin E. de Visser研究组报道了了解和逆转乳腺肿瘤驱动的骨髓生成重编程以减少转移性扩散。2025年5月8日，国际知名学术期刊《癌细胞》发表了这一成果。

该课题组研究人员结合单细胞、染色质和功能分析来揭示骨髓中肿瘤驱动的颗粒生成重编程，以及旨在逆转这一过程的干预研究。研究组观察到乳腺肿瘤以牺牲淋巴和红细胞生成为代价加速中性粒细胞谱系的承诺，而不刺激新的髓系谱系的发展。

此外，肿瘤导向的中性粒细胞免疫抑制印迹在造血早期就开始了。抗IL-1β治疗可使肿瘤诱导的颗粒生成正常化，减少中性粒细胞免疫抑制表型并减轻转移性扩散。总之，这些数据提供了异常的，肿瘤驱动的中性粒细胞分化途径，导致促进转移的慢性炎症，以及如何逆转它以减少转移扩散的分子见解。

研究人员表示，肿瘤诱导的中性粒细胞的系统性积累和极化到免疫抑制表型是转移形成的一个强有力的驱动因素。然而，乳腺肿瘤如何在分子水平上重编程颗粒生成，以及在中性粒细胞发育过程中肿瘤印记何时发生，仍未得到充分的研究。

附：英文原文

Title: Understanding and reversing mammary tumor-driven reprogramming of myelopoiesis to reduce metastatic spread

Author: Hannah Garner, Moreno Martinovic, Ning Qing Liu, Noor A.M. Bakker, Irene Querol Velilla, Cheei-Sing Hau, Kim Vrijland, Daphne Kaldenbach, Marleen Kok, Elzo de Wit, Karin E. de Visser

Issue&Volume: 2025-05-08

Abstract: Tumor-induced systemic accumulation and polarization of neutrophils to an immunosuppressive phenotype is a potent driver of metastasis formation. Yet, how mammary tumors reprogram granulopoiesis at the molecular level and when tumor imprinting occurs during neutrophil development remains underexplored. Here, we combined single-cell, chromatin and functional analyses to unravel the tumor-driven reprogramming of granulopoiesis in the bone marrow, along with intervention studies aimed at reversing this process. We observe that mammary tumors accelerate commitment to the neutrophil lineage at the expense of lymphopoiesis and erythropoiesis without stimulating the development of a novel myeloid lineage. Moreover, tumor-directed immunosuppressive imprinting of neutrophils starts early in hematopoiesis. Treatment with anti-IL-1β normalizes tumor-induced granulopoiesis, reducing neutrophil immunosuppressive phenotype and mitigating metastatic spread. Together, these data provide molecular insights into the aberrant, tumor-driven neutrophil differentiation pathway leading to metastasis-promoting chronic inflammation and how it can be reversed to reduce metastatic spread.

DOI: 10.1016/j.ccell.2025.04.007

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00166-7