Tanaka Shunya, Ohgidani Masahiro, Hata Nobuhiro, Inamine Shogo, Sagata Noriaki, Shirouzu Noritoshi, Mukae Nobutaka, Suzuki Satoshi O, Hamasaki Hideomi, Hatae Ryusuke, Sangatsuda Yuhei, Fujioka Yutaka, Takigawa Kosuke, Funakoshi Yusuke, Iwaki Toru, Hosoi Masako, Iihara Koji, Mizoguchi Masahiro, Kato Takahiro A
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Front Immunol. 2021 Jun 29;12:670131. doi: 10.3389/fimmu.2021.670131. eCollection 2021.
Targeting the unique glioma immune microenvironment is a promising approach in developing breakthrough immunotherapy treatments. However, recent advances in immunotherapy, including the development of immune checkpoint inhibitors, have not improved the outcomes of patients with glioma. A way of monitoring biological activity of immune cells in neural tissues affected by glioma should be developed to address this lack of sensitivity to immunotherapy. Thus, in this study, we sought to examine the feasibility of non-invasive monitoring of glioma-associated microglia/macrophages (GAM) by utilizing our previously developed induced microglia-like (iMG) cells. Primary microglia (pMG) were isolated from surgically obtained brain tissues of 22 patients with neurological diseases. iMG cells were produced from monocytes extracted from the patients' peripheral blood. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant correlation of the expression levels of representative markers for M1 and M2 microglia phenotypes between pMG and the corresponding iMG cells in each patient (Spearman's correlation coefficient = 0.5225, 0.0001). Synchronous upregulation of CD206 expression levels was observed in most patients with glioma (6/9, 66.7%) and almost all patients with glioblastoma (4/5, 80%). Therefore, iMG cells can be used as a minimally invasive tool for monitoring the disease-related immunological state of GAM in various brain diseases, including glioma. CD206 upregulation detected in iMG cells can be used as a surrogate biomarker of glioma.
针对独特的胶质瘤免疫微环境是开发突破性免疫治疗方法的一种有前景的途径。然而,免疫治疗的最新进展,包括免疫检查点抑制剂的开发,并未改善胶质瘤患者的预后。应该开发一种方法来监测受胶质瘤影响的神经组织中免疫细胞的生物活性,以解决对免疫治疗缺乏敏感性的问题。因此,在本研究中,我们试图通过利用我们先前开发的诱导型小胶质细胞样(iMG)细胞来研究非侵入性监测胶质瘤相关小胶质细胞/巨噬细胞(GAM)的可行性。从22例神经系统疾病患者手术获取的脑组织中分离出原代小胶质细胞(pMG)。iMG细胞由从患者外周血中提取的单核细胞产生。定量逆转录-聚合酶链反应(qRT-PCR)显示,每位患者的pMG和相应的iMG细胞之间,M1和M2小胶质细胞表型的代表性标志物表达水平具有显著相关性(斯皮尔曼相关系数 = 0.5225,P = 0.0001)。在大多数胶质瘤患者(6/9,66.7%)和几乎所有胶质母细胞瘤患者(4/5,80%)中观察到CD206表达水平同步上调。因此,iMG细胞可作为一种微创工具,用于监测包括胶质瘤在内的各种脑部疾病中GAM的疾病相关免疫状态。在iMG细胞中检测到的CD206上调可作为胶质瘤的替代生物标志物。