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心脏黏液瘤中的衰老、免疫微环境和血管生成

Senescence, immune microenvironment, and vascularization in cardiac myxomas.

作者信息

Karpathiou Georgia, Dumollard Jean Marc, Camy Florian, Sramek Viviana, Dridi Maroa, Picot Tiphanie, Mobarki Mousa, Peoc'h Michel

机构信息

Pathology Department, University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France.

Pathology Department, University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France.

出版信息

Cardiovasc Pathol. 2021 May-Jun;52:107335. doi: 10.1016/j.carpath.2021.107335. Epub 2021 Mar 21.

DOI:10.1016/j.carpath.2021.107335
PMID:33762213
Abstract

AIMS

Cardiac myxomas are rare tumors of incompletely elucidated pathogenesis. The aim of this study is to explore the possible presence of a senescence phenotype in cardiac myxomas, associated with an inflammatory and vasculogenic tumor microenvironment.

METHODS AND RESULTS

This is a retrospective study of 29 cardiac myxomas with immunohistochemical detection of various inflammatory, vascular, and senescence markers. We show that all myxomas contain tumor cells in senescence overexpressing p16, and a fraction of senescent endothelial cells. Macrophages are the principal inflammatory cell population, followed by cytotoxic T cells, with fewer plasma cells, mastocytes, and B lymphocytes. These populations are found in different intratumoral localizations. Larger tumor volume is associated with a lower percentage of myxoid matrix, higher cellularity, higher macrophage, and lower number of mast cells as well as higher PD-L1 expression by inflammatory cells. Higher vascular density is associated with higher percentage of B cells, a lower number of macrophages and higher number of mastocytes, and lower PD-L1 expression by inflammatory cells. Tumors with higher vascular density and higher cellularity show higher amounts of p16 senescent endothelial cells.

CONCLUSIONS

Myxoma tumor cells are in senescence and reside inside a tumor microenvironment with a distinct inflammatory profile rich in macrophages and cytotoxic T cells, and a rich vasculature, probably attributed to a senescence-associated secretory phenotype.

摘要

目的

心脏黏液瘤是一种发病机制尚未完全阐明的罕见肿瘤。本研究的目的是探讨心脏黏液瘤中可能存在的衰老表型,以及与炎症和血管生成性肿瘤微环境的相关性。

方法与结果

这是一项对29例心脏黏液瘤的回顾性研究,通过免疫组织化学检测各种炎症、血管和衰老标志物。我们发现所有黏液瘤均含有过表达p16的衰老肿瘤细胞以及一部分衰老内皮细胞。巨噬细胞是主要的炎症细胞群体,其次是细胞毒性T细胞,浆细胞、肥大细胞和B淋巴细胞较少。这些细胞群体分布于肿瘤内不同部位。肿瘤体积较大与黏液样基质比例较低、细胞密度较高、巨噬细胞比例较高、肥大细胞数量较少以及炎症细胞中PD-L1表达较高相关。血管密度较高与B细胞比例较高、巨噬细胞数量较少、肥大细胞数量较多以及炎症细胞中PD-L1表达较低相关。血管密度较高且细胞密度较高的肿瘤显示p16衰老内皮细胞数量较多。

结论

黏液瘤肿瘤细胞处于衰老状态,存在于具有独特炎症特征(富含巨噬细胞和细胞毒性T细胞)和丰富血管系统的肿瘤微环境中,这可能归因于衰老相关分泌表型。

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