研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

胶质母细胞瘤中的颅脑功能性淋巴单位。

Cranioencephalic functional lymphoid units in glioblastoma.

发表日期:2024 Jul 31
作者: Celia Dobersalske, Laurèl Rauschenbach, Yichao Hua, Christoph Berliner, Anita Steinbach, Anika Grüneboom, Konstantinos D Kokkaliaris, Dieter H Heiland, Pia Berger, Sarah Langer, Chin L Tan, Martin Stenzel, Somaya Landolsi, Flora Weber, Marvin Darkwah Oppong, Rudolf A Werner, Hanah Gull, Thomas Schröder, Thomas Linsenmann, Andreas K Buck, Matthias Gunzer, Martin Stuschke, Kathy Keyvani, Michael Forsting, Martin Glas, Jonathan Kipnis, Dennis A Steindler, Hans Christian Reinhardt, Edward W Green, Michael Platten, Alpaslan Tasdogan, Ken Herrmann, Florian Rambow, Igor Cima, Ulrich Sure, Björn Scheffler
来源: NATURE MEDICINE

摘要:

脑肿瘤的生态系统被认为是免疫抑制的,但我们目前的知识可能并不完整。在这里,我们分析了来自患有胶质母细胞瘤或非恶性颅内疾病的患者的临床细胞和组织标本,报告说,与未经治疗的胶质母细胞瘤肿瘤相比,颅骨(CB)骨髓在初次诊断时就含有活跃的淋巴群体。临床和解剖成像、单细胞分子和免疫细胞分析以及肿瘤反应性的量化确定了 CB 中的 CD8 T 细胞克隆型,这些克隆型也在肿瘤中发现。这些的特点是根植于整个 T 细胞发育谱的急性和持久的抗肿瘤反应。与远端骨髓相比,靠近肿瘤的 CB 生态位显示表达淋巴出口标记物 S1PR1 的肿瘤反应性 CD8 效应子类型的频率增加。与此一致,CXCR4放射性标记的颅骨增强可以作为替代标记,表明与改善的无进展生存期的局灶性关联。本研究的数据主张保存和进一步利用这些颅脑单元用于胶质母细胞瘤的临床护理。© 2024。作者。
The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition to treatment-naive glioblastoma tumors, harbors active lymphoid populations at the time of initial diagnosis. Clinical and anatomical imaging, single-cell molecular and immune cell profiling and quantification of tumor reactivity identified CD8+ T cell clonotypes in the CB that were also found in the tumor. These were characterized by acute and durable antitumor response rooted in the entire T cell developmental spectrum. In contrast to distal bone marrow, the CB niche proximal to the tumor showed increased frequencies of tumor-reactive CD8+ effector types expressing the lymphoid egress marker S1PR1. In line with this, cranial enhancement of CXCR4 radiolabel may serve as a surrogate marker indicating focal association with improved progression-free survival. The data of this study advocate preservation and further exploitation of these cranioencephalic units for the clinical care of glioblastoma.© 2024. The Author(s).