fig1

Figure 1. Schematic diagram outlining complex pro- and anti-inflammatory interplay within epithelial ovarian cancer microenvironment. Created with Biorender.com. Tumour cells recognised by APC, from which tumour antigens are presented to naïve CD4+ T cells, triggering T cell differentiation into Th1, Th2, Treg cell subclones (and other Th subsets – not pictured). Cytotoxic CD8+ T cells are recruited to TME via chemokines such as CCL3 and CXCL9 and are activated. Once activated, it releases granzyme and perforin to lyse cells directly. Th1 cells have dual action by secreting cytokines including IL-2 and IL-12, further activating CD8+ T cells to directly kill tumour cells as well as secreting IFN-gamma to suppress angiogenesis. Th2 assists eosinophil recruitment via IL-4 and IL-13 cytokine release, which assist in antitumour response. Treg cells suppress DC maturation and mute CD8+ T cell response by secreting inhibitory cytokines IL-10, IL-35, and TGF-β in response to regulate inflammatory response. M1 TAM, a pro-inflammatory type, is involved in tumour destruction, while M2 TAM exhibits immunosuppressive effects allowing tumour migration and invasion by releasing factors including endothelin-1, VEGF and TNF-alpha to induce tumour angiogenesis. CD4⁺ T cells bind to B cells via major histocompatibility II complex to induce antibody formation via the adaptive immune system. APC: antigen-presenting cell; MDSC: Myeloid-derived suppressor cells; IL: Interleukin; TGF-β: transforming growth factor-beta; TNF: Tumour necrosis factor; CCL: Chemokine (C-C Motif); CXCL: Chemokine (C-X-C Motif); IDO: Indoleamine 2,3-dioxygenase; Th: T-Helper; M1 and M2 TAM: Tumour-associated macrophages; MMP: matrix metalloproteinase; E: eosinophil; VEGF: vascular endothelial growth factor; TF: tissue factor; PGE2: prostaglandin E2; IFN: interferon; β-FGF: beta-fibroblast growth factor.