Chasing Immune Checkpoint Inhibitors in Ovarian Cancer: Novel Combinations and Biomarker Discovery

SIMPLE SUMMARY: Immune checkpoint inhibitors (ICIs) have been investigated in epithelial ovarian cancer in first-line and recurrent settings. When used as a single agent or in combination with chemotherapy, they have largely failed to improve patients’ outcome and thus, have not entered routine use in clinical practice. However, there are signs of promising activity in some early and late-phase clinical trials, combining immune checkpoint inhibitors with effective targeted agents, such as those targeting the tumor blood supply (antiangiogenics) or when taking advantage of impaired intra-cellular machinery that are unable to repair major cell damage (for example with poly-ADP-ribose inhibitors (PARP)). Further research is still needed to define predictive biomarkers that can identify patients more likely to respond to ICI combinations. New targets and treatment strategies are under investigation to define if and how immunotherapy can be incorporated into the treatment of epithelial ovarian cancer. ABSTRACT: A deep understanding of the tumor microenvironment and the recognition of tumor-infiltrating lymphocytes as a prognostic factor have resulted in major milestones in immunotherapy that have led to therapeutic advances in treating many cancers. Yet, the translation of this knowledge to clinical success for ovarian cancer remains a challenge. The efficacy of immune checkpoint inhibitors as single agents or combined with chemotherapy has been unsatisfactory, leading to the exploration of alternative combination strategies with targeted agents (e.g., poly-ADP-ribose inhibitors (PARP)and angiogenesis inhibitors) and novel immunotherapy approaches. Among the different histological subtypes, clear cell ovarian cancer has shown a higher sensitivity to immunotherapy. A deeper understanding of the mechanism of immune resistance within the context of ovarian cancer and the identification of predictive biomarkers remain central discovery benchmarks to be realized. This will be critical to successfully define the precision use of immune checkpoint inhibitors for the treatment of ovarian cancer.