Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice

Abstract

International audienc

TGF-β and VEGF cooperatively control the immunotolerant tumor environment and the efficacy of cancer immunotherapies

“…This environment is in large part imprinted by Tregs (14)(15)(16). At the time of tumor emergence in mice, competition arises between antitumor Tregs and Teffs (17).…”

The Early Pregnancy Human Placenta Shares Hypomethylation Patterns Characteristic of Solid Tumors

“…We also investigated links between cancer/placenta patterns of methylation and gene expression profiles in cancer. 4 We report here that the early pregnancy human placenta is hypomethylated compared to that later in pregnancy. This hypomethylation is organized into megabase-scale domains that frequently overlap with hypomethylated block regions observed in solid tumors [8,9].…”

“…Our analyses also pointed to immune-related genes which were down-modulated in colon tumors, including CD69 and CCL5. This last observation could be explained by the presence within the immune infiltrate of suppressive subpopulations such as regulatory T cells (Tregs), M2 macrophages or myeloid-derived suppressive cells (MDSC), that have previously been linked to tolerance induction both in cancer and pregnancy [2,4,41,42]. Our approach thus suggests a means for identifying genes potentially regulated by similar epigenetic mechanisms during pregnancy and neoplastic transformation.…”

“…Over the 20th century, successive technological innovations have allowed the characterization of striking similarities between placental and cancer cells. The microscope initially allowed the observation of common phenotypes [16,17], and later modern biochemistry and molecular biology allowed the characterization of molecular circuits underlying these similarities: thus, we now know that placental cells, even though they do not possesses the somatically altered genomes characteristic of cancer cells, rely on hallmark cancer molecular programs to establish pregnancy 9 [1][2][3][4]18]. More recently, independent studies in cancer biology and placenta biology have suggested similarities between epigenetic patterns in placental and cancer cells [5,6].…”

“…They also promote angiogenesis, while surviving hypoxia, to establish fetal/maternal exchange of nutrients, gases and wastes. Moreover, as 50% of the placental genome has paternal origin, placental cells have to evade the maternal immune system [1][2][3][4].…”