Estrogens and the Schrödinger’s Cat in the Ovarian Tumor Microenvironment

SIMPLE SUMMARY: Ovarian cancer is a complex pathology for which we require effective screening and therapeutical strategies. Apart from the cancer cell portion, there exist plastic immune and non-immune cell populations, jointly constituting the context-adaptive tumor microenvironment, which is pivotal in tumorigenesis. Estrogens might be synthesized in the ovarian tumor tissue and actively contribute to the shaping of an immunosuppressive microenvironment. Current immune therapies have limited effectiveness as a multitude of factors influence the outcome. A thorough understanding of the ovarian cancer biology is crucial in the efforts to reestablish homeostasis. ABSTRACT: Ovarian cancer is a heterogeneous disease affecting the aging ovary, in concert with a complex network of cells and signals, together representing the ovarian tumor microenvironment. As in the “Schrödinger’s cat” thought experiment, the context-dependent constituents of the—by the time of diagnosis—well-established tumor microenvironment may display a tumor-protective and -destructive role. Systemic and locally synthesized estrogens contribute to the formation of a pro-tumoral microenvironment that enables the sustained tumor growth, invasion and metastasis. Here we focus on the estrogen biosynthetic and metabolic pathways in ovarian cancer and elaborate their actions on phenotypically plastic, estrogen-responsive, aging immune cells of the tumor microenvironment, altogether highlighting the multicomponent-connectedness and complexity of cancer, and contributing to a broader understanding of the ovarian cancer biology.