Hypoxia coordinates the spatial landscape of myeloid cells within glioblastoma to affect outcome
Hypoxia coordinates the spatial landscape of myeloid cells within glioblastoma to affect outcome
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DOI：
10.1101/2023.06.30.547190
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发表时间：
2023-06
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通讯作者：
M. Haley;Leoma D. Bere;James Minshull;Sokratia Georgaka;N. Garcia-Martin;Gareth Howell;D. Coope;F. Roncaroli;Andrew King;D. Wedge;Stuart M Allan;Omar N. Pathmanaban;D. Brough;K. Couper
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作者：
M. Haley;Leoma D. Bere;James Minshull;Sokratia Georgaka;N. Garcia-Martin;Gareth Howell;D. Coope;F. Roncaroli;Andrew King;D. Wedge;Stuart M Allan;Omar N. Pathmanaban;D. Brough;K. Couper
髓系细胞在胶质母细胞瘤(GBM)中非常普遍，以一系列表型和激活状态存在。我们目前对肿瘤微环境(TME)决定因素的了解有限，这些决定因素影响了GBM中不同髓系细胞群体的定位和功能。在这里，我们利用单细胞和空间转录方法的正交成像质量细胞术来识别和绘制人类GBM肿瘤微环境(TME)中的各种髓系群体。我们的结果表明，不同的髓系群体在GBM TME中有不同的和可重复的区划模式，这是由组织缺氧、局部趋化因子信号以及不同的同型和异型细胞相互作用驱动的。随后，我们根据已鉴定的髓系细胞群的组成，确定了基底膜中特定的肿瘤亚区，这些亚区与患者的生存有关。我们的结果提供了对GBM中髓系细胞亚群的空间组织的新见解，以及这如何预测临床结果。TEASER多模式映射显示，胶质母细胞瘤中髓系细胞的空间组织影响疾病结局。
Myeloid cells are highly prevalent in glioblastoma (GBM), existing in a spectrum of phenotypic and activation states. We currently have limited knowledge of the tumour microenvironment (TME) determinants that influence the localisation and the functions of the diverse myeloid cell populations in GBM. Here we have utilised orthogonal imaging mass cytometry with single cell and spatial transcriptomics approaches to identify and map the various myeloid populations in the human GBM tumour microenvironment (TME). Our results show that different myeloid populations have distinct and reproducible compartmentalisation patterns in the GBM TME that is driven by tissue hypoxia, regional chemokine signalling, and varied homotypic and heterotypic cellular interactions. We subsequently identified specific tumour sub-regions in GBM, based upon composition of identified myeloid cell populations, that were linked to patient survival. Our results provide new insight into the spatial organisation of myeloid cell sub populations in GBM, and how this is predictive of clinical outcome. Teaser Multi-modal mapping reveals that the spatial organisation of myeloid cells in glioblastoma impacts disease outcome.