Abstract
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.
Highlights
Complex and multiple immune related mechanisms allow the uterus and the placenta to mount powerful responses to infection, but at the same time to tolerate fetus’ paternal alloantigens, both inside the mother’s womb and in the blood circulation of both mother and fetus [1]
In our placental/decidual materials from spontaneous abortions in first trimester, trophoblast cells surrounded by lymphocytes with natural killer (NK) characteristics and CD56++ or CD16++ staining were abundant
We found no evidence of significant decidual natural killer cells (dNK) cells in the primary breast cancer of our patient, and only limited presence in decidua/placenta at 39-weeks of gestation, there are a number of interesting publications that suggest a very special role for these NK subtypes, both in pregnant uterine and malignant microenvironment
Summary
Complex and multiple immune related mechanisms allow the uterus and the placenta to mount powerful responses to infection (bacterial, protozoal and viral), but at the same time to tolerate fetus’ paternal alloantigens, both inside the mother’s womb and in the blood circulation of both mother and fetus [1]. The multinucleated syncytiotrophoblast cells form the external layer and are terminally differentiated These cells are involved in fetomaternal nutrient exchanges and endocrine functions www.impactjournals.com/oncotarget (such as β-human chorionic gonadotropic). EVT cells have a proliferative and invasive phenotype, migrating through the syncytiotrophoblast into the uterine wall to anchor the placenta beginning around day 14 after implantation [3]. These EVT cells display a phenotype strikingly similar to cancer cells, with capacity for proliferation, migration and establishment of blood supply, making them a compelling model for oncologic comparison [4]
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