BACKGROUND Neurofibromatosis type 2 (NF2) patients uniformly develop multiple schwannomas. The tumor-microenvironment (TME) is associated with hypoxia and consists of immunosuppressive cells, including regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). The hypoxic TME of NF2 schwannomas remains unclear. In addition, no comparative study has investigated immunosuppressive cells in NF2 and sporadic schwannomas. METHODS In 22 NF2 and 21 sporadic schwannomas, we analyzed the immunohistochemistry for Ki-67, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2, platelet derived growth factor receptor-beta (PDGFR-β), programmed cell death-1 (PD-1)/ programmed cell death ligand-1 (PD-L1), Foxp3, CD163, CD3, and CD8 to assess the immunosuppressive TME. RESULTS Most vessels in sporadic schwannomas exhibited slight or negative VEGFR1 and 2 expressions with pericytes coverage. In contrast, large vessels in NF2 schwannomas exhibited strong VEGFR1 and 2 expressions without pericytes. The number of CD3+, CD8+, and CD163+ cells was significantly higher in NF2 schwannomas than in sporadic ones. The expression of PD-L1 and nestin positive cell ratio was higher in NF2 schwannomas than that in sporadic ones. The number of CD163+ cells, nestin positive cell ratio, and HIF-1α expression were significantly associated with shorter progression-free survival in NF2 schwannomas. CONCLUSIONS This study presents the clinicopathological features of the differences in immunosuppressive cells and the expression of immune checkpoint molecules between NF2 and sporadic schwannomas. Hypoxic TME was first detected in NF2-schwannomas, which was associated with the tumor progression.

中文翻译：

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神经纤维瘤病2型神经鞘瘤和偶发性神经鞘瘤患者低氧免疫抑制性微环境的差异。

背景技术2型神经纤维瘤病（NF2）患者均匀发展为多发神经鞘瘤。肿瘤微环境（TME）与缺氧有关，由免疫抑制细胞组成，包括调节性T细胞（Tregs）和肿瘤相关巨噬细胞（TAMs）。尚不清楚NF2神经鞘瘤的低氧TME。此外，尚无比较研究调查NF2和散发性神经鞘瘤中的免疫抑制细胞。方法在22例NF2和21例偶发性神经鞘瘤中，我们分析了Ki-67，低氧诱导因子-1α（HIF-1α），血管内皮生长因子受体1（VEGFR1）和VEGFR2，血小板衍生生长因子受体β（ PDGFR-β），程序性细胞死亡1（PD-1）/程序性细胞死亡配体1（PD-L1），Foxp3，CD163，CD3和CD8来评估免疫抑制性TME。结果散发性神经鞘瘤中的大多数血管表现出轻度或阴性的VEGFR1和2表达，并有周细胞覆盖。相反，NF2神经鞘瘤中的大血管表现出很强的VEGFR1和2表达，而没有周细胞。NF2神经鞘瘤中CD3 +，CD8 +和CD163 +细胞的数量显着高于散发性神经鞘瘤。NF2神经鞘瘤中PD-L1的表达和巢蛋白阳性细胞比例高于散发性神经鞘瘤。CD163 +细胞的数量，巢蛋白阳性细胞比例和HIF-1α表达与NF2神经鞘瘤的较短的无进展生存期显着相关。结论这项研究提出了NF2和散发性神经鞘瘤之间免疫抑制细胞和免疫检查点分子表达的差异的临床病理特征。