Hassel Bjørnar, Niehusmann Pitt, Halvorsen Bente, Dahlberg Daniel
Department of Neurohabilitation, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Front Oncol. 2022 Jul 29;12:846674. doi: 10.3389/fonc.2022.846674. eCollection 2022.
Cystic glioblastomas are aggressive primary brain tumors that may both destroy and displace the surrounding brain tissue as they grow. The mechanisms underlying these tumors' destructive effect could include exposure of brain tissue to tumor-derived cytokines, but quantitative cytokine data are lacking. Here, we provide quantitative data on leukocyte markers and cytokines in the cyst fluid from 21 cystic glioblastomas, which we compare to values in 13 brain abscess pus samples. The concentration of macrophage/microglia markers sCD163 and MCP-1 was higher in glioblastoma cyst fluid than in brain abscess pus; lymphocyte marker sCD25 was similar in cyst fluid and pus, whereas neutrophil marker myeloperoxidase was higher in pus. Median cytokine levels in glioblastoma cyst fluid were high (pg/mL): TNF-α: 32, IL-6: 1064, IL-8: 23585, tissue factor: 28, the chemokine CXCL1: 639. These values were not significantly different from values in pus, pointing to a highly pro-inflammatory glioblastoma environment. In contrast, levels of IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12, and IL-13 were higher in pus than in glioblastoma cyst fluid. Based on the quantitative data, we show for the first time that the concentrations of cytokines in glioblastoma cyst fluid correlate with blood leukocyte levels, suggesting an important interaction between glioblastomas and the circulation. Preoperative MRI of the cystic glioblastomas confirmed both destruction and displacement of brain tissue, but none of the cytokine levels correlated with degree of brain tissue displacement or peri-tumoral edema, as could be assessed by MRI. We conclude that cystic glioblastomas are highly pro-inflammatory environments that interact with the circulation and that they both displace and destroy brain tissue. These observations point to the need for neuroprotective strategies in glioblastoma therapy, which could include an anti-inflammatory approach.
囊性胶质母细胞瘤是侵袭性原发性脑肿瘤，生长过程中可破坏并取代周围脑组织。这些肿瘤产生破坏作用的潜在机制可能包括脑组织暴露于肿瘤源性细胞因子，但缺乏定量细胞因子数据。在此，我们提供了21例囊性胶质母细胞瘤囊液中白细胞标志物和细胞因子的定量数据，并与13例脑脓肿脓液样本中的数值进行比较。胶质母细胞瘤囊液中巨噬细胞/小胶质细胞标志物sCD163和MCP-1的浓度高于脑脓肿脓液；淋巴细胞标志物sCD25在囊液和脓液中相似，而中性粒细胞标志物髓过氧化物酶在脓液中更高。胶质母细胞瘤囊液中细胞因子的中位数水平较高（pg/mL）：TNF-α：32，IL-6：1064，IL-8：23585，组织因子：28，趋化因子CXCL1：639。这些数值与脓液中的数值无显著差异，表明胶质母细胞瘤环境具有高度促炎作用。相比之下，脓液中IFN-γ、IL-1β、IL-2、IL-4、IL-10、IL-12和IL-13的水平高于胶质母细胞瘤囊液。基于定量数据，我们首次表明胶质母细胞瘤囊液中的细胞因子浓度与血液白细胞水平相关，提示胶质母细胞瘤与循环系统之间存在重要相互作用。囊性胶质母细胞瘤的术前MRI证实了脑组织的破坏和移位，但通过MRI评估，没有一种细胞因子水平与脑组织移位程度或瘤周水肿相关。我们得出结论，囊性胶质母细胞瘤是高度促炎的环境，与循环系统相互作用，既能取代又能破坏脑组织。这些观察结果表明，胶质母细胞瘤治疗中需要采取神经保护策略，其中可能包括抗炎方法。
