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Immunosuppressive Tumor Microenvironment Status and Histological Grading of Endometrial Carcinoma
Cancer Microenvironment Pub Date : 2019-05-27 , DOI: 10.1007/s12307-019-00225-1
Julie Antomarchi 1 , Damien Ambrosetti 1 , Charlotte Cohen 1 , Jérôme Delotte 1 , Anne Chevallier 1 , Babou Karimdjee-Soilihi 1, 2 , Mélanie Ngo-Mai 1 , Annie Schmid-Alliana 1 , Heidy Schmid-Antomarchi 1, 3
Affiliation  

The recent successes of new cancer immunotherapy approaches have led to investigate their relevance in the context of the Endometrial Carcinoma (EC). These therapies, that take the tumor-induced immunosuppressive microenvironment into account, target the tumor immune escape, in particular the inhibitory receptors involved in the regulation of the effector T cells’ activity (immune checkpoints). The aim of this study was to identify, in ECs, differences in intergrades immune status that could contribute to the differences in tumor aggressiveness, and could also be used as theranostic tools. The immune status of tumors was assessed by quantitative real-time PCR. We analyzed the expression of specific genes associated to specific leukocytes subpopulations and the expression of reporting genes associated with the tumor escape/resistance. This study highlights significant differences in the EC intergrades immune status especially the tumor-infiltrating cell types and their activation status as well as in the molecular factors produced by the environment. The immune microenvironment of grade 1 ECs hints at a robust tumoricidal milieu while that of higher grades is more evocative of a tolerogenic milieu. This genes-based immunological monitoring of tumors that easily highlights significant intergrade differences relating to the density, composition and functional state of the leukocyte infiltrate, could give solid arguments for choosing the best therapeutic options, especially those targeting immune checkpoints. Moreover it could enable an easy adaptation of individual treatment approaches for each patient.



中文翻译:

子宫内膜癌的免疫抑制性肿瘤微环境现状及组织学分级

新的癌症免疫治疗方法最近取得的成功引发了人们对它们在子宫内膜癌 (EC) 背景下的相关性的研究。这些疗法考虑了肿瘤诱导的免疫抑制微环境,针对肿瘤免疫逃逸,特别是参与调节效应 T 细胞活性(免疫检查点)的抑制性受体。本研究的目的是确定 EC 中跨级免疫状态的差异,这些差异可能导致肿瘤侵袭性的差异,也可以用作治疗诊断工具。通过实时定量PCR评估肿瘤的免疫状态。我们分析了与特定白细胞亚群相关的特定基因的表达以及与肿瘤逃逸/抵抗相关的报告基因的表达。这项研究强调了内皮细胞间质免疫状态的显着差异,特别是肿瘤浸润细胞类型及其激活状态以及环境产生的分子因子的显着差异。 1 级 EC 的免疫微环境暗示着强大的杀肿瘤环境,而更高级别的 EC 更容易让人联想到耐受性环境。这种基于基因的肿瘤免疫学监测很容易突出与白细胞浸润的密度、组成和功能状态相关的显着的级间差异,可以为选择最佳治疗方案,特别是针对免疫检查点的方案提供坚实的论据。此外,它可以轻松地适应每位患者的个体治疗方法。

更新日期:2019-05-27
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