Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland; Neuroscience Research Center, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.
Department of Oncology, University of Lausanne, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne 1011, Switzerland; Agora Cancer Research Centre Lausanne, Lausanne 1011, Switzerland.
Cell. 2023 Oct 12;186(21):4546-4566.e27. doi: 10.1016/j.cell.2023.08.043. Epub 2023 Sep 27.
Neutrophils are abundant immune cells in the circulation and frequently infiltrate tumors in substantial numbers. However, their precise functions in different cancer types remain incompletely understood, including in the brain microenvironment. We therefore investigated neutrophils in tumor tissue of glioma and brain metastasis patients, with matched peripheral blood, and herein describe the first in-depth analysis of neutrophil phenotypes and functions in these tissues. Orthogonal profiling strategies in humans and mice revealed that brain tumor-associated neutrophils (TANs) differ significantly from blood neutrophils and have a prolonged lifespan and immune-suppressive and pro-angiogenic capacity. TANs exhibit a distinct inflammatory signature, driven by a combination of soluble inflammatory mediators including tumor necrosis factor alpha (TNF-ɑ) and Ceruloplasmin, which is more pronounced in TANs from brain metastasis versus glioma. Myeloid cells, including tumor-associated macrophages, emerge at the core of this network of pro-inflammatory mediators, supporting the concept of a critical myeloid niche regulating overall immune suppression in human brain tumors.
中性粒细胞是循环系统中丰富的免疫细胞，经常大量浸润肿瘤。然而，它们在不同癌症类型中的确切功能仍不完全清楚，包括在脑微环境中。因此，我们研究了脑胶质瘤和脑转移患者肿瘤组织中的中性粒细胞，并与外周血相匹配，并在此描述了对这些组织中中性粒细胞表型和功能的首次深入分析。人类和小鼠的正交分析策略表明，与血液中性粒细胞相比，脑肿瘤相关中性粒细胞（TAN）具有显著差异，具有延长的寿命以及免疫抑制和促血管生成能力。TAN 表现出独特的炎症特征，由包括肿瘤坏死因子-α (TNF-ɑ) 和铜蓝蛋白在内的可溶性炎症介质组合驱动，而源自脑转移的 TAN 比源自脑胶质瘤的 TAN 更为显著。髓样细胞，包括肿瘤相关巨噬细胞，出现在这个促炎介质网络的核心，支持调节人脑肿瘤整体免疫抑制的关键髓样生态位的概念。
