Division of Neurosurgery, Department of Surgery, St. Michael's Hospital, Toronto, ON, Canada.
Sci Rep. 2020 Jun 3;10(1):9065. doi: 10.1038/s41598-020-65365-7.
Modulation of tumor microenvironment is an emerging frontier for new therapeutics. However in meningiomas, the most frequent adult brain tumor, the correlation of microenvironment with tumor phenotype is scarcely studied. We applied a variety of systems biology approaches to bulk tumor transcriptomics to explore the immune environments of both skull base and convexity (hemispheric) meningiomas. We hypothesized that the more benign biology of skull base meningiomas parallels the relative composition and activity of immune cells that oppose tumor growth and/or survival. We firstly applied gene co-expression networks to tumor bulk transcriptomics from 107 meningiomas (derived from 3 independent studies) and found immune processes to be the sole biological mechanism correlated with anatomical location while correcting for tumour grade. We then derived tumor immune cell fractions from bulk transcriptomics data and examined the immune cell-cytokine interactions using a network-based approach. We demonstrate that oncolytic Gamma-Delta T cells dominate skull base meningiomas while mast cells and neutrophils, known to play a role in oncogenesis, show greater activity in convexity tumors. Our results are the first to suggest the importance of tumor microenvironment in meningioma biology in the context of anatomic location and immune landscape. These findings may help better inform surgical decision making and yield location-specific therapies through modulation of immune microenvironment.
肿瘤微环境的调控是新疗法的一个新兴前沿。然而，在脑膜瘤中，最常见的成人脑肿瘤，微环境与肿瘤表型的相关性几乎没有研究。我们应用了各种系统生物学方法对脑膜瘤的大量肿瘤转录组进行研究，以探索颅底和大脑半球脑膜瘤的免疫环境。我们假设颅底脑膜瘤的生物学特性更为良性，这与对抗肿瘤生长和/或存活的免疫细胞的相对组成和活性有关。我们首先将基因共表达网络应用于来自 107 例脑膜瘤（来自 3 个独立研究）的肿瘤大量转录组学，并发现免疫过程是唯一与解剖位置相关的生物学机制，同时纠正了肿瘤分级。然后，我们从大量转录组学数据中提取肿瘤免疫细胞分数，并使用基于网络的方法研究免疫细胞-细胞因子相互作用。我们证明，溶瘤性γ-δ T 细胞在颅底脑膜瘤中占主导地位，而肥大细胞和中性粒细胞，已知在肿瘤发生中起作用，在大脑半球肿瘤中表现出更大的活性。我们的研究结果首次表明，在解剖位置和免疫图谱的背景下，肿瘤微环境在脑膜瘤生物学中的重要性。这些发现可能有助于更好地为手术决策提供信息，并通过调节免疫微环境产生特定于位置的治疗方法。
