原发性脑肿瘤中的免疫细胞浸润和炎症景观

原发性恶性脑肿瘤占所有脑肿瘤的三分之一以上，尽管进行了分子研究以鉴定癌症驱动器突变，但由于肿瘤内异质性高，目前可用的治疗选择具有挑战性。此外，免疫抑制和炎症性肿瘤微环境增强了癌症的进展。 Therefore, we defined an immune and inflammatory profiling of meningioma and glial tumours to elucidate the role of the immune infiltration in these cancer types.Using tissue microarrays of 158 brain tumour samples, we assessed CD3, CD4, CD8, CD20, CD138, Granzyme B (GzmB), 5-Lipoxygenase (5-LOX), Programmed Death-Ligand 1通过免疫组织化学（IHC）（IHC）（IHC）（PD-L1），O-6-甲基鸟氨酸-DNA甲基转移酶（MGMT）和转谷氨酰胺酶2（TG2）表达（IHC）。 IHC结果使用Spearman相关矩阵将其相关。使用在GEPIA2上获得的公共数据集（GBM）（GBM）和较低级别胶质瘤（LGG）同类群的转录表达，相关和总生存（OS）分析进行评估。在十个标记中，在至少一个评估的CD3，CD3，CD3，CD4，gbs and gbs中，十个标记中的IHC表达显着差异很大。相关矩阵分析表明，5-LOX和GZMB表达在脑膜瘤和GBMS中均相关，而5-LOX表达在脑膜瘤和星形胶质细胞瘤同胞中与TG2显着且正相关。通过TCGA-GBM和LGG数据集的相关分析证实了这些发现。与对照组织相比，mRNA水平的分析表明，GBM中CD3（CD3D，CD3E）和CD138（SDC1）表达显着增加。在肿瘤样品中，CD4和5-lox（ALOX5）mRNA水平明显比在GBM和LGG中的正常组织中要高得多。在GBM队列中，GZMB（GZMB），SDC1和MGMT基因表达预测总生存率较差（OS）。此外，在LGG队列中，CD3（CD3D，CD3E，CD3G），CD8（CD8A），GZMB，CD20（MS4A1），SDC1，PD-L1，Alox5，Alox5和TG2（TGM2）（TGM2）基因的表达增加与较差的OS相关联，OS的表达与较差的相关性相关联，GZMB，CD8A（CD8A），GZMB，CD20（MS4A1）（MS4A1）（PD-L1，ALOX5和TG2（TGM2）基因都具有阳性和显着的相关性。蛋白质水平。需要进一步评估以了解5-lox和免疫浸润在神经胶质瘤进展中的相互作用。

Primary malignant brain tumours are more than one-third of all brain tumours and despite the molecular investigation to identify cancer driver mutations, the current therapeutic options available are challenging due to high intratumour heterogeneity. In addition, an immunosuppressive and inflammatory tumour microenvironment strengthens cancer progression. Therefore, we defined an immune and inflammatory profiling of meningioma and glial tumours to elucidate the role of the immune infiltration in these cancer types.Using tissue microarrays of 158 brain tumour samples, we assessed CD3, CD4, CD8, CD20, CD138, Granzyme B (GzmB), 5-Lipoxygenase (5-LOX), Programmed Death-Ligand 1 (PD-L1), O-6-Methylguanine-DNA Methyltransferase (MGMT) and Transglutaminase 2 (TG2) expression by immunohistochemistry (IHC). IHC results were correlated using a Spearman correlation matrix. Transcript expression, correlation, and overall survival (OS) analyses were evaluated using public datasets available on GEPIA2 in Glioblastoma (GBM) and Lower Grade Glioma (LGG) cohorts.Seven out of ten markers showed a significantly different IHC expression in at least one of the evaluated cohorts whereas CD3, CD4 and 5-LOX were differentially expressed between GBMs and astrocytomas. Correlation matrix analysis revealed that 5-LOX and GzmB expression were associated in both meningiomas and GBMs, whereas 5-LOX expression was significantly and positively correlated to TG2 in both meningioma and astrocytoma cohorts. These findings were confirmed with the correlation analysis of TCGA-GBM and LGG datasets. Profiling of mRNA levels indicated a significant increase in CD3 (CD3D, CD3E), and CD138 (SDC1) expression in GBM compared to control tissues. CD4 and 5-LOX (ALOX5) mRNA levels were significantly more expressed in tumour samples than in normal tissues in both GBM and LGG. In GBM cohort, GzmB (GZMB), SDC1 and MGMT gene expression predicted a poor overall survival (OS). Moreover, in LGG cohort, an increased expression of CD3 (CD3D, CD3E, CD3G), CD8 (CD8A), GZMB, CD20 (MS4A1), SDC1, PD-L1, ALOX5, and TG2 (TGM2) genes was associated with worse OS.Our data have revealed that there is a positive and significant correlation between the expression of 5-LOX and GzmB, both at RNA and protein level. Further evaluation is needed to understand the interplay of 5-LOX and immune infiltration in glioma progression.