Figure 3.

The immunosuppressive ovarian tumor microenvironment and the contribution of estrogens to its formation. Local and systemic estrogens reaching the ovarian tumor tissue affect various cells of the growingly immunosuppressive microenvironment. Immune cells are responsive to estrogens through receptors. Estrogens contribute to M2-like activation of macrophages and their accumulation in the tumor tissue. Furthermore, estrogens might enhance pathologic myelopoiesis, recruitment of immature myeloid cells (IMCs) to the tumor tissue and their conversion to myeloid derived suppressor cells (MDSCs). Moreover, estrogens stimulate the expansion of regulatory T (T_reg) cells, and might promote tolerogenic phenotype in dendritic cells (DCs). In addition, these immune cells of the microenvironment influence the activity of each other, for example, MDSCs might commit to M2-like tumor associated macrophages (TAMs) and T_regs, which in turn inhibit DCs antigen-presenting actions. A plethora of soluble factors, such as TGF-β, IL-10 released in the microenvironment further stimulate the formation of an immunosuppressive microenvironment that inhibits effector CD8⁺ cells and NK cells. Consequently, CD8⁺ T lymphocytes present as less mature, produce less granzyme and perforine, and overexpress PD-1, which drives them to exhaustion. The inhospitable microenvironment restricts the NKs infiltration and induces their apoptosis, altogether leading to tumor escape from immune destruction. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) (accessed on 7 May 2021).