Ventricular opening and cerebrospinal fluid circulation accelerate the biodegradation process of carmustine wafers suggesting their immunomodulation potential in the human brain
Ventricular opening and cerebrospinal fluid circulation accelerate the biodegradation process of carmustine wafers suggesting their immunomodulation potential in the human brain
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DOI：
10.1007/s11060-022-04078-5
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发表时间：
2022-07
影响因子：
3.9
通讯作者：
Ichiyo Shibahara;Y. Shibahara;H. Hagiwara;Takashi Watanabe;Yasushi Orihashi;H. Handa;M. Inukai;T. Hide;Y. Yasui;T. Kumabe
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作者：
Ichiyo Shibahara;Y. Shibahara;H. Hagiwara;Takashi Watanabe;Yasushi Orihashi;H. Handa;M. Inukai;T. Hide;Y. Yasui;T. Kumabe
目的在胶质母细胞瘤手术中开放心室系统通常是必要的，但其对胶质母细胞瘤肿瘤微环境的影响尚不清楚。卡莫司汀晶片的植入使药物能够直接递送到肿瘤部位；然而，硅片生物降解过程的确切机制尚不清楚，现有数据仅限于体内非人类哺乳动物研究。我们假设脑室开度影响了胶质母细胞瘤的降解过程和肿瘤微环境。方法本研究纳入30例胶质母细胞瘤患者。21例患者在初次手术时行卡莫司汀晶圆植入。所有的患者在复发后都进行了反复的手术切除，以比较与晶圆植入相关的病理变化。使用CD68、TMEM119、CD163、IBA1、BIN1和CD31抗体进行免疫组织化学分析，以突出小胶质细胞、巨噬细胞和肿瘤血管性，定量评分结果与临床、分子和手术变量相关，包括心室开放的影响。结果卡莫司汀植入组肿瘤内tmem119阳性小胶质细胞明显减少（P = 0.0002）。简单和多元回归分析显示，tmem119阳性小胶质细胞的减少与手术和打开心室系统的间隔时间较长有关。年龄、甲基化o6 -甲基鸟嘌呤DNA甲基转移酶启动子表达与手术切除程度无相关性。结论本研究结果强烈提示生物材料可能具有免疫调节能力，其免疫调节能力受到心室打开手术的显著影响。此外，我们的数据强调了脑室开口在周围人脑中的病理生理效应，特别是在晶圆植入后。
PurposeOpening the ventricular system during glioblastoma surgery is often necessary, but the consequent effect on the tumor microenvironment of glioblastoma remains unknown. Implantation of carmustine wafer enables direct drug delivery to the tumor site; however, the exact mechanism of the wafer’s biodegradation process is unclear, and the available data is limited to in vivo non-human mammalian studies. We hypothesized that the ventricular opening affects the degradation process of the wafer and the glioblastoma tumor microenvironment.MethodsThis study included 30 glioblastoma patients. 21 patients underwent carmustine wafer implantation during initial surgery. All patients underwent repeated surgical resection upon recurrence, allowing for pathological comparison of changes associated with wafer implantation. Immunohistochemical analyses were performed using CD68, TMEM119, CD163, IBA1, BIN1, and CD31 antibodies to highlight microglia, macrophages, and tumor vascularity, and the quantitative scoring results were correlated with clinical, molecular, and surgical variables, including the effect of the ventricular opening.ResultsThe carmustine wafer implanted group presented significantly less TMEM119-positive microglia within the tumor (P = 0.0002). Simple and multiple regression analyses revealed that the decrease in TMEM119-positive microglia was correlated with longer intervals between surgeries and opened ventricular systems. No correlation was observed between age, methylated O6-methylguanine DNA methyltransferase promoter expression, and the extent of surgical resection.ConclusionsOur study findings strongly suggest that biomaterials may possess immunomodulation capacity, which is significantly impacted by the ventricular opening procedure. Furthermore, our data highlights the pathophysiological effects of the ventricular opening within the surrounding human brain, especially after the wafer implantation.