Immune pathway through endometriosis to ovarian cancer

Figure 1 Depiction of immune surveillance evasion mechanisms in endometriosis. A: Illustration of FAS/FASL-mediated apoptosis in cytotoxic lymphocytes and TNF-α-induced ectopic endometrial cell apoptosis resistance; B: Key molecular factors contributing to dysregulated apoptosis signaling in endometriosis. CD8+ T cell: Cytotoxic T-cells; ECC: Ectopic Endometrial Cells; Erβ: Estrogen receptor β; FAS (CD95): Cluster of Differentiation 95; FASL: FAS Ligand; IL-1β: Interleukin-1β; IL-8: Interleukin-8; MΦ: Macrophage; NCOA-1: Nuclear receptor coactivator 1; NK cell: Natural killer cell; TNF-α: Tumor necrosis factor-alpha.

Figure 2 Overview of immune dysregulation similarities between on endometriosis and ovarian cancer. IL-1: Interleukin-1; IL-1B: Interleukin-1β; IL-4: Interleukin-4; IL-6: Interleukin-6; IL-8: Interleukin-8; IL-10: Interleukin-10; E2: Prostaglandin E2; ER-a: Estrogen Receptor Alpha; M1/M2: Macrophages; NK: Natural killer cell; TAM: Tumor-associated macrophages; Th1/Th2/Th17: T helper cells; TNF: Tumor Necrosis Factor; TNF-a: Tumor Necrosis Factor Alpha; TNF-B: Tumor Necrosis Factor Beta; ROS: Reactive oxygen species; VEGF: Vascular endothelial growth factor.

Figure 3 Some of the current immunotherapy approaches of treatment to ovarian cancer. Anti-CTLA-4: Cytotoxic T-Lymphocyte Associated Protein 4 Antibody; Anti-PD1: Programmed Cell death Protein 1 Antibody; Anti PD-L1: Programmed Death-ligand 1 Antibody; CAR-T cells: Chimeric Antigen Receptor-T cells; PARP: Poly Adenosine Diphosphate-Ribose Polymerase; PD-1: Programmed Cell death Protein 1; PD-L1: Programmed Death-ligand 1.

Figure 4 Illustration of anti-CD47-based immunotherapy. CD47 is a glycoprotein that is very present in the tumor environment and exerts its inhibitory activity by binding to its counter-receptor, the signal regulatory protein-α (SIRPα), expressed in macrophages. It reduces phagocytosis by these, which culminates in the progression of the tumor microenvironment. It is highly expressed patients with endometriosis. A: CD47 binding to SIRPα inhibits phagocytosis; B: Anti-CD47 blocks the binding between CD47 and SIRPα, allowing phagocytosis to occur. Anti-CD47: Integrin-associated protein Antibody; CD47: Integrin-associated protein; MΦ: Macrophage; OC cells: Ovarian Cancer cells; SIRPα: signal regulatory protein alpha.

Figure 5 Illustration of anti-CSF-1R-based immunotherapy. The colony-stimulating factor-1 receptor (CSF-1R) is a receptor that exists in several human cells during homeostasis, but is overexpressed in tumor-associated macrophages in ovarian cancer. The use of a monoclonal antibody directed at blocking CSF-1R in cancer patients, aims to manipulate the activity of TAMs, reducing tumor-associated macrophages in patients, as well as an increase in the levels of TCD8/CD4 cells in animal models. Anti-CSF-1R: Colony-Stimulating Factor 1 receptor Antibody CSF-1: Colony-Stimulating Factor 1; CSF-1R: Colony-Stimulating Factor 1 receptor; M2 TAM Φ: Tumor-associated macrophages M2; OC cell: Ovarian Cancer cells; TAM Φ: Tumor-associated macrophages.