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Inflammatory Infiltrate and Angiogenesis in Mantle Cell Lymphoma.
Translational Oncology ( IF 5 ) Pub Date : 2020-02-29 , DOI: 10.1016/j.tranon.2020.100744
Tiziana Annese 1 , Giuseppe Ingravallo 2 , Roberto Tamma 1 , Michelina De Giorgis 1 , Eugenio Maiorano 2 , Tommasina Perrone 3 , Francesco Albano 3 , Giorgina Specchia 3 , Domenico Ribatti 1
Affiliation  

Mantle cell lymphoma (MCL) is an aggressive and rare B-cell non-Hodgkin lymphoma classified in two clinicopathological subtypes according to SOX11 expression and mutation state of immunoglobulin variable region heavy chain (IgVH) gene. The transcription factor SOX11, overexpressed in 78%-93% of MCL patients, plays a central role in modulating tumor microenvironment prosurvival signals and angiogenic genes. In this work, we have explored the lymph node microenvironment of three subgroups of MCL patients classified according to SOX11 expression as negative, light, and strong. CD34+ microvessels, CD4+ and CD8+ T-lymphocytes, CD68+ and CD163+ macrophages, and the oncogene p53 expression were evaluated by immunohistochemistry. Moreover, STAT3 mRNA expression was analyzed by RNA-scope assay.

Our results confirmed increased angiogenesis in the sample of patients positive to SOX11 compared to the negative ones and demonstrated that angiogenesis and SOX11 expression positively correlate to a higher T-lymphocytes inflammatory infiltrate. On the contrary, angiogenesis and SOX11 expression negatively correlate with macrophage's inflammatory infiltrate and p53 expression. STAT3 mRNA expression level was not relevant concerning angiogenesis or SOX11 expression. Overall, our data indicate that, in MCL, SOX11 expression is associated with increased angiogenesis and a high CD4+ and CD8+ T-cell infiltration, which are not sustained by CD163+ macrophages infiltrate and p53 expression.



中文翻译:

外套细胞淋巴瘤的炎症浸润和血管生成。

套细胞淋巴瘤(MCL)是一种侵袭性罕见B细胞非霍奇金淋巴瘤,根据SOX11表达和免疫球蛋白可变区重链(IgVH)基因的突变状态分为两种临床病理亚型。在78%-93%的MCL患者中过表达的转录因子SOX11在调节肿瘤微环境的生存信号和血管生成基因中起着核心作用。在这项工作中,我们研究了按SOX11表达分类为阴性,轻和强的MCL患者的三个亚组的淋巴结微环境。CD34 +微血管,CD4 +和CD8 + T淋巴细胞,CD68 +和CD163 +通过免疫组织化学评估巨噬细胞和癌基因p53表达。此外,STAT3 mRNA表达通过RNA范围分析进行分析。

我们的结果证实,与阴性的患者相比,对SOX11阳性的患者的样本中血管生成增加,并证明血管生成和SOX11的表达与较高的T淋巴细胞炎症浸润呈正相关。相反,血管生成和SOX11表达与巨噬细胞的炎性浸润和p53表达负相关。STAT3 mRNA表达水平与血管生成或SOX11表达无关。总的来说,我们的数据表明,在MCL中,SOX11的表达与血管生成的增加以及CD4 +和CD8 + T细胞的高浸润有关,而CD163 +巨噬细胞浸润和p53表达并不能维持这种表达。

更新日期:2020-02-29
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