Tamura Ryota, Ohara Kentaro, Sasaki Hikaru, Morimoto Yukina, Kosugi Kenzo, Yoshida Kazunari, Toda Masahiro
Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
World Neurosurg. 2018 Dec;120:e601-e610. doi: 10.1016/j.wneu.2018.08.133. Epub 2018 Aug 27.
Vascular endothelial growth factor (VEGF)-A and VEGF receptor expression in the peritumoral brain zone (PBZ) differs from that in the tumor core (TC) of glioblastoma. To date, no comparative study has investigated the expression of immunosuppressive cells in the PBZ and TC of glioblastoma.
In 10 patients with newly diagnosed glioblastoma, we used immunohistochemistry to analyze the expression of VEGF-A, hypoxia-inducible factor-1α, programmed cell death-1 (PD-1), Foxp3, CD163, CD4, and CD8 to assess the immunosuppressive microenvironment.
The number of Foxp3 and CD163 cells was significantly greater in the TC than in the PBZ and correlated with greater expression of hypoxia-inducible factor-1α and VEGF-A in the TC than in the PBZ. The number of CD8 T cells was lower in the TC than in the PBZ, and the TC had more PD-1CD8 T cells compared with the PBZ. These results suggest that the hypoxic condition could be associated with PD-1 expression on lymphocytes, the distribution of Foxp3 regulatory T cells and CD163 tumor-associated macrophages.
The present study reports the first clinicopathologic features of the differences in immunosuppressive cells and the expression of immune checkpoint molecules between the TC and PBZ of glioblastoma.
胶质母细胞瘤瘤周脑区(PBZ)中的血管内皮生长因子(VEGF)-A和VEGF受体表达与肿瘤核心(TC)不同。迄今为止,尚无比较研究调查胶质母细胞瘤PBZ和TC中免疫抑制细胞的表达情况。
在10例新诊断的胶质母细胞瘤患者中,我们使用免疫组织化学分析VEGF-A、缺氧诱导因子-1α、程序性细胞死亡蛋白-1(PD-1)、叉头框蛋白3(Foxp3)、CD163、CD4和CD8的表达,以评估免疫抑制微环境。
TC中Foxp3和CD163细胞的数量显著多于PBZ,且与TC中缺氧诱导因子-1α和VEGF-A的表达高于PBZ相关。TC中CD8 T细胞的数量低于PBZ,且与PBZ相比,TC中有更多的PD-1⁺CD8 T细胞。这些结果表明,缺氧状态可能与淋巴细胞上PD-1的表达、Foxp3调节性T细胞和CD163肿瘤相关巨噬细胞的分布有关。
本研究首次报道了胶质母细胞瘤TC和PBZ之间免疫抑制细胞差异及免疫检查点分子表达的临床病理特征。