Driving Immune Responses in the Ovarian Tumor Microenvironment

Abstract

Ovarian cancer is the leading cause of death among gynecological neoplasms, with an estimated 14,000 deaths in 2019. First-line treatment options center around a taxane and platinum-based chemotherapy regimen. However, many patients often have recurrence due to late stage diagnoses and acquired chemo-resistance. Recent approvals for bevacizumab and poly (ADP-ribose) polymerase inhibitors have improved treatment options but effective treatments are still limited in the recurrent setting. Immunotherapy has seen significant success in hematological and solid malignancies. However, effectiveness has been limited in ovarian cancer. This may be due to a highly immunosuppressive tumor microenvironment and a lack of tumor-specific antigens. Certain immune cell subsets, such as regulatory T cells and tumor-associated macrophages, have been implicated in ovarian cancer. Consequently, therapies augmenting the immune response, such as immune checkpoint inhibitors and dendritic cell vaccines, may be unable to properly enact their effector functions. A better understanding of the various interactions among immune cell subsets in the peritoneal microenvironment is necessary to develop efficacious therapies. This review will discuss various cell subsets in the ovarian tumor microenvironment, current immunotherapy modalities to target or augment these immune subsets, and treatment challenges.

Comprehensive Landscape of Ovarian Cancer Immune Microenvironment Based on Integrated Multi-Omics Analysis

“…The TME has an essential role in suppressing or enhancing the immune response (6). Recent studies have shown that an immunosuppressive TME is a major obstacle to successful implementation of tumor immunotherapy in OC patients (7,8). Therefore, understanding how the immune microenvironment of OC may hinder effective immune attack could guide the prediction of OC patients and promote more practical applications of immunotherapy in OC.…”

Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives

“…However, limited benefits have emerged in OC, even leading to premature termination due to the futility of some studies. Different components of the OC tumor microenvironment (TME) contribute to this failure, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), T-cells, cytokines, and soluble factors [37][38][39][40]. MDSCs exert immunosuppressive functions, such as the inhibition of T-effector and natural killer (NK)-cells, and are induced under proinflammatory cytokines, IFNγ, tumor necrosis factor-alpha (TNFα), interleukin (IL)-6 [41].…”

Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives.

“…However, limited benefits have emerged in the OC, even leading to the premature termination for the futility of some studies. Different components of the OC tumor microenvironment (TME) contribute to this failure, such as myeloid-derived suppressor cells (MDSCs), tumorassociated macrophages (TAMs), T-cells, cytokines, and soluble factors [37][38][39][40]. MDSCs exert immunosuppressive functions, such as the inhibition of T-effector and natural killer (NK)-cells, and are induced under pro-inflammatory cytokines, IFNγ, tumor necrosis factor-alpha (TNFα), interleukin (IL)-6 [41].…”