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Association between Inflammatory Infiltrates and Isolated Monosomy 22/del(22q) in Meningiomas

机译:脑膜瘤中炎性浸润与孤立单体型22 / del(22q)之间的关联

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摘要

Meningiomas contain highly variable levels of infiltrating tissue macrophages (TiMa) and other immune cells. In this study we investigated the potential association between the number and immunophenotype of inflammatory and other immune cells infiltrating the tumor as evaluated by multiparameter flow cytometry, and the clinico-biological, cytogenetic and gene expression profile (GEP) of 75 meningioma patients. Overall, our results showed a close association between the amount and cellular composition of the inflammatory and other immune cell infiltrates and the cytogenetic profile of the tumors. Notably, tumors with isolated monosomy 22/del(22q) showed greater numbers of TiMa, NK cells and (recently)-activated CD69+ lymphocytes versus meningiomas with diploid and complex karyotypes. In addition, in the former cytogenetic subgroup of meningiomas, tumor-infiltrating TiMa also showed a more activated and functionally mature phenotype, as reflected by a greater fraction of CD69+, CD63+, CD16+ and CD33+ cells. GEP at the mRNA level showed a unique GEP among meningiomas with an isolated monosomy 22/del(22q) versus all other cases, which consisted of increased expression of genes involved in inflammatory/immune response, associated with an M1 TiMa phenotype. Altogether, these results suggest that loss of expression of specific genes coded in chromosome 22 (e.g. MIF) is closely associated with an increased homing and potentially also anti-tumoral effect of TiMa, which could contribute to explain the better outcome of this specific good-prognosis cytogenetic subgroup of meningiomas.
机译:脑膜瘤包含高度可变的浸润组织巨噬细胞(TiMa)和其他免疫细胞。在这项研究中,我们调查了通过多参数流式细胞术评估的炎症和其他浸润肿瘤的免疫细胞的数量与免疫表型之间的潜在关联,以及75名脑膜瘤患者的临床生物学,细胞遗传学和基因表达谱(GEP)。总的来说,我们的结果表明炎性和其他免疫细胞浸润的数量和细胞组成与肿瘤的细胞遗传学特征之间有着密切的联系。值得注意的是,与二倍体和复杂核型的脑膜瘤相比,孤立的22 / del(22q)单体肿瘤显示出更多的TiMa,NK细胞和(最近)激活的CD69 + 淋巴细胞。另外,在前脑膜瘤的细胞遗传学亚组中,肿瘤浸润性TiMa也表现出更活化和功能成熟的表型,这表现为更大比例的CD69 + ,CD63 + ,CD16 + 和CD33 + 细胞。与所有其他病例相比,在mRNA水平上的GEP在脑膜瘤中表现出独特的GEP,具有孤立的22 / del(22q)单体性,包括与M1 TiMa表型有关的炎症/免疫反应相关基因的表达增加。总而言之,这些结果表明,第22号染色体编码的特定基因(例如MIF)表达的丧失与TiMa的归巢增加以及潜在的抗肿瘤作用密切相关,这可能有助于解释这种特异性好基因的更好结果。预后脑膜瘤的细胞遗传学亚组。

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