Faculty of Health: Medicine, Dentistry and Human Sciences, The Institute of Translational and Stratified Medicine, University of Plymouth, The John Bull Building, Plymouth Science Park, Research Way, Plymouth PL6 8BU, UK.
Department of Neurosurgery, University Hospitals Plymouth NHS Trust, Derriford Road, Plymouth PL6 8DH, UK.
Int J Mol Sci. 2020 Feb 13;21(4):1273. doi: 10.3390/ijms21041273.
The majority of meningiomas are grade I, but some grade I tumours are clinically more aggressive. Recent advances in the genetic study of meningiomas has allowed investigation into the influence of genetics on the tumour microenvironment, which is important for tumorigenesis. We have established that the endpoint genotyping method Kompetitive Allele Specific PCR (KASP™) is a fast, reliable method for the screening of meningioma samples into different non-NF2 mutational groups using a standard real-time PCR instrument. This genotyping method and four-colour flow cytometry has enabled us to assess the variability in the largest immune cell infiltrate population, M2 macrophages (CD45HLA-DRCD14CD163) in 42 meningioma samples, and to suggest that underlying genetics is relevant. Further immunohistochemistry analysis comparing mutants to WHO grade I NF2-negative samples showed significantly lower levels of CD163-positive activated M2 macrophages in meningiomas with mutated signifying a more immunosuppressive tumour microenvironment in NF2 meningiomas. Our data suggested that underlying tumour genetics play a part in the development of the immune composition of the tumour microenvironment. Stratifying meningiomas by mutational status and correlating this with their cellular composition will aid in the development of new immunotherapies for patients.
大多数脑膜瘤为 I 级，但一些 I 级肿瘤在临床上更具侵袭性。脑膜瘤遗传学研究的最新进展使人们能够研究遗传学对肿瘤微环境的影响，这对于肿瘤发生很重要。我们已经证实，终点基因分型方法 Kompetitive Allele Specific PCR（KASP™）是一种快速、可靠的方法，可使用标准实时 PCR 仪器将脑膜瘤样本分为不同的非 NF2 突变组。这种基因分型方法和四色流式细胞术使我们能够评估最大的免疫细胞浸润群体 M2 巨噬细胞（CD45HLA-DRCD14CD163）在 42 个脑膜瘤样本中的变异性，并表明潜在的遗传学是相关的。进一步的免疫组织化学分析比较突变型与 WHO 分级 I NF2 阴性样本显示，NF2 脑膜瘤中突变型 的 CD163 阳性激活 M2 巨噬细胞水平显著降低，表明 NF2 脑膜瘤中的肿瘤微环境更具免疫抑制性。我们的数据表明，潜在的肿瘤遗传学在肿瘤微环境的免疫组成的发展中起作用。通过突变状态对脑膜瘤进行分层，并将其与细胞组成相关联，将有助于为患者开发新的免疫疗法。
