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上皮-间质转化对乳腺癌免疫格局的影响

Impact of Epithelial-Mesenchymal Transition on the Immune Landscape in Breast Cancer.

作者信息

Khadri Fatima-Zohra, Issac Marianne Samir Makboul, Gaboury Louis Arthur

机构信息

Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, QC H3T 1J4, Canada.

Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada.

出版信息

Cancers (Basel). 2021 Oct 12;13(20):5099. doi: 10.3390/cancers13205099.

Abstract

The impact of epithelial-mesenchymal transition (EMT) signature on the immune infiltrate present in the breast cancer tumor microenvironment (TME) is still poorly understood. Since there is mounting interest in the use of immunotherapy for the treatment of subsets of breast cancer patients, it is of major importance to understand the fundamental tumor characteristics which dictate the inter-tumor heterogeneity in immune landscapes. We aimed to assess the impact of EMT-related markers on the nature and magnitude of the inflammatory infiltrate present in breast cancer TME and their association with the clinicopathological parameters. Tissue microarrays were constructed from 144 formalin-fixed paraffin-embedded invasive breast cancer tumor samples. The protein expression patterns of Snail, Twist, ZEB1, N-cadherin, Vimentin, GRHL2, E-cadherin, and EpCAM were examined by immunohistochemistry (IHC). The inflammatory infiltrate in the TME was assessed semi-quantitatively on hematoxylin and eosin (H&E)-stained whole sections and was characterized using IHC. The inflammatory infiltrate was more intense in poorly differentiated carcinomas and triple-negative carcinomas in which the expression of E-cadherin and GRHL2 was reduced, while EpCAM was overexpressed. Most EMT-related markers correlated with plasma cell infiltration of the TME. Taken together, our findings reveal that the EMT signature might impact the immune response in the TME.

摘要

上皮-间质转化(EMT)特征对乳腺癌肿瘤微环境(TME)中免疫浸润的影响仍知之甚少。鉴于免疫疗法在乳腺癌患者亚群治疗中的应用兴趣日益浓厚,了解决定免疫格局中肿瘤间异质性的基本肿瘤特征至关重要。我们旨在评估EMT相关标志物对乳腺癌TME中炎性浸润的性质和程度的影响,以及它们与临床病理参数的关联。组织微阵列由144个福尔马林固定石蜡包埋的浸润性乳腺癌肿瘤样本构建而成。通过免疫组织化学(IHC)检测Snail、Twist、ZEB1、N-钙黏蛋白、波形蛋白、GRHL2、E-钙黏蛋白和EpCAM的蛋白表达模式。在苏木精和伊红(H&E)染色的全切片上对TME中的炎性浸润进行半定量评估,并使用IHC进行特征描述。在低分化癌和三阴性癌中,炎性浸润更为强烈,其中E-钙黏蛋白和GRHL2的表达降低,而EpCAM过表达。大多数EMT相关标志物与TME中的浆细胞浸润相关。综上所述,我们的研究结果表明EMT特征可能会影响TME中的免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d307/8533811/f1e47848d19d/cancers-13-05099-g001.jpg

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