Figure 2.

Representative cell types and their interactions in the tumor microenvironment (TME) of ovarian cancer. Cancer cells and mesothelium cells secrete pro-inflammatory cytokines and chemokines, including macrophage chemoattractant protein-1 (MCP1/CCL2), which recruits tumor associated macrophages (TAM) to the peritoneum. Increased infiltration of TAMs in the peritoneal TME not only promotes ovarian cancer cell invasion but also induces an immunosuppressive environment that suppresses the function of T cells, dendritic cells (DCs), and natural killer (NK) cells and activates the function of regulatory T cells (Tregs). Mesothelial cells are the first barrier to this process; however, the bidirectional cross-talk between cancer and mesothelial cells results in mesothelial clearance and invasion of the sub-mesothelial layers. Myeloid-derived suppressor cells (MDSCs) are attracted to the tumor site in response to growth factors and inflammatory cytokines/chemokines that are secreted by ovarian cancer cells. MDSCs could suppress T cell function, maintain the ovarian cancer stem cell pool, and interact with adipocytes. In the ovarian TME, blood vessel structure is modulated by a plethora of factors that are secreted by ovarian cancer cells, MDSCs, and cancer associated fibroblasts (CAFs). Molecular cross-talk between cancer cells and CAFs in the ovarian TME produce a pro-inflammatory TME and promote tumor progression. The bidirectional interaction between omental adipocytes and cancer cells promote dedifferentiation and reprogramming of adipocytes into cancer-associated adipocytes (CAAs). In turn, cancer cells absorbing fat rapidly promote tumor proliferation.