Bronchud Miguel H, Tresserra Francesc, Zantop Bernat Serra
Institut Bellmunt Oncologia, Hospital Universitari Dexeus, Grupo Quiron Salud, Barcelona, 08028 Spain.
Servicio de Anatomía Patológica y Citología, Hospital Universitari Dexeus, Grupo Quiron Salud, Barcelona, 08028 Spain.
Oncotarget. 2017 Dec 19;9(5):6028-6041. doi: 10.18632/oncotarget.23488. eCollection 2018 Jan 19.
Microenvironmental properties are thought to be responsible for feto-maternal tolerance. Speculatively, ectopic expression of placental gene programs might also be related to cancer cells' ability to escape from immune vigilance mechanisms during carcinogenesis and cancer progression. Recently, we published the first human genomic evidence of similar immune related gene expression profiles in both placenta (placenta and decidual tissue) and cancer (both primary and metastatic) in the same patient with lymph-node positive breast carcinoma during pregnancy. Here we report the first epigenomic analysis of these tissue samples and describe their main findings, with respect to immune related genes regulation (over or under expressed) in cancer cells with regards placental tissues. We confirm significant similarities, and hierarchical clustering (both unsupervised and supervised), in CpG island methylation patterns between decidual/placental and cancer microenvironments, which cannot be easily explained by simple models or unique pathways. Several different cell types are probably involved in these complex immune regulation mechanisms. Cancers may somehow "hijack" gene programs evolved over millions of years to allow for feto-maternal tolerance in placental mammals in order to escape from immune vigilance and spread locally or to distant sites.
微环境特性被认为是母婴耐受的原因。据推测,胎盘基因程序的异位表达也可能与癌细胞在致癌过程和癌症进展中逃避免疫监视机制的能力有关。最近,我们发表了首例人类基因组证据,证明在一名妊娠期间淋巴结阳性乳腺癌患者的胎盘(胎盘和蜕膜组织)和癌症(原发和转移)中存在相似的免疫相关基因表达谱。在此,我们报告对这些组织样本的首次表观基因组分析,并描述其主要发现,涉及癌细胞相对于胎盘组织中免疫相关基因的调控(过表达或低表达)。我们证实,蜕膜/胎盘与癌症微环境之间的CpG岛甲基化模式存在显著相似性以及层次聚类(无监督和有监督),这无法用简单模型或独特途径轻易解释。几种不同的细胞类型可能参与了这些复杂的免疫调节机制。癌症可能以某种方式“劫持”了数百万年进化而来的基因程序,以实现胎盘哺乳动物中的母婴耐受,从而逃避免疫监视并在局部或远处扩散。