Breast cancers co-opt normal mechanisms of tolerance to promote immune evasion and metastasis

Normal developmental processes, such as those seen during embryonic development and postpartum mammary gland involution, can be reactivated by cancer cells to promote immune suppression, tumor growth, and metastatic spread. In mammalian embryos, paternal-derived antigens are at risk of being recognized as foreign by the maternal immune system. Suppression of the maternal immune response toward the fetus, which is mediated in part by the trophoblast, is critical to ensure embryonic survival and development. The postpartum mammary microenvironment also exhibits immunosuppressive mechanisms accompanying the massive cell death and tissue remodeling that occurs during mammary gland involution. These normal immunosuppressive mechanisms are paralleled during malignant transformation, where tumors can develop neoantigens that may be recognized as foreign by the immune system. To circumvent this, tumors can dedifferentiate and co-opt immune-suppressive mechanisms normally utilized during fetal tolerance and postpartum mammary involution. In this review, we discuss those similarities and how they can inform our understanding of cancer progression and metastasis.