Immunotherapy in the Treatment of Platinum-Resistant Ovarian Cancer: Current Perspectives

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The gold standard therapeutic approach is a combination of surgery plus chemotherapy. Unfortunately, 80% of patients with EOC suffer recurrence within 2-years and the overall response rate for platinum-resistant epithelial ovarian cancer to cytotoxic chemotherapy or poly-(adenosine diphosphate)-ribose polymerase (PARP) inhibitor is modest. New therapies are needed to improve overall survival. The role of immunotherapy has been established in endometrial and cervical cancers, however its effective use in EOC has been limited due to the intrinsic genomics and micro-immune environment associated with EOC. Studies evaluating immunotherapy, largely immune checkpoint inhibitors (ICI), have shown limited activity, yet some patients benefit greatly. Thus, significant efforts must be devoted to finding new strategies for the use of immunotherapy/immunomodulatory drugs (IMiDs). Immunotherapy has a well-tolerated safety profile; however, cost-effectiveness can be an obstacle. The aim of this article is to review the most recent research into the use of IMiDs in patients with platinum-resistant epithelial ovarian cancer.

Platinum-resistance in epithelial ovarian cancer: an interplay of epithelial–mesenchymal transition interlinked with reprogrammed metabolism

“…As most of the ECM components in the study facilitated the infiltration of dendritic cells, may indicate essential role of remodeled ECM components in facilitating dendritic cell function which contributes in a significant way to antitumor response. However, approaches to use immunotherapy have not shown success in primary HGSOC or platinum resistant HGSOC patients [ 64 , 65 ]. Potential reasons for the lack of immunotherapy response in HGSOC patients may include abundance of immunosuppressive factors in ovarian TME such as infiltration of a variety of immunosuppressive cells such as myeloid-derived suppressor cells (MDSC), cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAM) and Tregs.…”

“…In addition, the density of intraepithelial CD8 + T cells was shown to inversely correlate with the expression of PD-L1 on tumor cells, suggesting that the expression of PD-L1 on tumor cells may result in the exclusion of CD8 + T-cell in the tumors [ 66 ]. Some of these factors may indicate limited activity of immune check point inhibitors in treating chemonaive and platinum resistant ovarian cancer patients [ 65 ].…”

Immunotherapy for Ovarian Cancer: Disappointing or Promising?

“…Peptide vaccines involve the injection of peptide immunogenic stimulators into the body, which are processed by antigen-presenting cells (APCs) and presented to basal immune response cells. This mechanism aids in recognizing and eliminating cancer cells expressing prevalent antigens, such as CA-125, MUC1, p53, and CEA . P53 immunotherapy takes advantage of the inadequate tolerance of tumor cells to activate the immune system and cause the destruction of p53-overexpressing tumor cells.…”

“…This mechanism aids in recognizing and eliminating cancer cells expressing prevalent antigens, such as CA-125, MUC1, p53, and CEA. 43 P53 immunotherapy takes advantage of the inadequate tolerance of tumor cells to activate the immune system and cause the destruction of p53-overexpressing tumor cells. The existence of a dominant p53 mutation generates tumor-specific antigens, making p53 a suitable target for tumor vaccines.…”

Correlation between immune‑related adverse events and treatment efficacy of anti‑PD1 immunotherapy in patients with esophageal squamous cell carcinoma

“…The ligand-receptor pairs that negatively regulate T-cell activation, including cytotoxic T-lymphocyte antigen 4 (CTLA4)-B7 and programmed death-1 (PD-1)-programmed death ligand 1 (PD-L1), are called 'immune checkpoints' (10). Immune checkpoint inhibitors (ICIs) have drastically improved the survival rate of patients with several tumor types, including melanoma, non-small cell lung cancer (NSCLC), renal cell cancer, ovarian cancer, and gastrointestinal tract cancers (11)(12)(13)(14)(15)(16). Patients with high PD-L1 expression appear to benefit more from ICI treatment for certain types of cancer (11,15).…”