Navigating the immunosuppressive brain tumor microenvironment using spatial biology

Samuel S. Widodo , Marija Dinevska , Stanley S. Stylli , Adriano L. Martinelli , Marianna Rapsomaniki , Theo Mantamadiotis
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Abstract

With the application of spatial biology, the detection and identification of the diverse cell types present in the tumor microenvironment, including specific immune subsets, is possible at single cell resolution. Since spatial biology analysis of tumor tissue allows multiple biological parameters to be measured, including cell type, cell number, cell state, as well as the precise location and the spatial relationship of every cell to other cells and histopathological hallmarks, a vast amount of data is generated. The power of this is realized when correlating the spatial biology data with clinical data for each patient, from which the tissue was collected during biopsy or surgery, conducted as part of the patient's diagnosis and treatment. Aside from the enormous leap in chemistry and molecular biology technology required to develop the analytical tools for spatial biology, collection, analysis of cells in the tumor microenvironment has been possible only with the development of computational tools capable of deciphering tumor tissue complexity to predict tumor evolution and response to treatment and the role of immune cells in regulating tumor biology. Here we describe how spatial biology analysis, combined with computational analysis have been used to deconstruct the complexity of the brain tumor microenvironment and shed light on why brain tumors exhibit extreme immunosuppression. We also discuss how the understanding gained using spatial biology has shed light on how tumor immunosuppression can be overcome.

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利用空间生物学为免疫抑制性脑肿瘤微环境导航
应用空间生物学技术,可以以单细胞分辨率检测和识别肿瘤微环境中存在的各种细胞类型,包括特定的免疫亚群。由于对肿瘤组织的空间生物学分析可测量多种生物参数,包括细胞类型、细胞数量、细胞状态,以及每个细胞的精确位置及其与其他细胞和组织病理学特征的空间关系,因此可生成大量数据。将空间生物学数据与每位患者的临床数据(组织是在活组织检查或手术中采集的,作为患者诊断和治疗的一部分)关联起来,就能发现这些数据的威力。除了开发空间生物学分析工具所需的化学和分子生物学技术的巨大飞跃之外,只有开发出能够破译肿瘤组织复杂性的计算工具,才能对肿瘤微环境中的细胞进行收集和分析,从而预测肿瘤的演变、对治疗的反应以及免疫细胞在调节肿瘤生物学中的作用。在这里,我们将介绍如何利用空间生物学分析结合计算分析来解构脑肿瘤微环境的复杂性,并揭示脑肿瘤表现出极端免疫抑制的原因。我们还讨论了如何利用空间生物学获得的理解来阐明如何克服肿瘤免疫抑制。
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Immunoinformatics (Amsterdam, Netherlands)
Immunoinformatics (Amsterdam, Netherlands) Immunology, Computer Science Applications
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