Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

SIMPLE SUMMARY: Most endometrial cancer patients are diagnosed at an early stage, receive standard treatment, and survive well. Ovarian cancer has no specific symptoms and usually escapes diagnosis until the patient has advanced disease. This disease results in the highest number of deaths of gynecologic cancers. Current treatments for gynecologic cancers in the advanced stage are not sufficiently effective for good outcome in most patients. This review discusses two novel treatments, which are immune checkpoint inhibitor antibodies that block immune checkpoint molecules cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed death-1 (PD-1) in patients. The antibody blocking of CTLA-4 or PD-1 alone is promising treatment for some categories of advanced disease endometrial cancer, but it has little effect against ovarian cancer. Our study primarily discusses the status of clinical trials for these two diseases and the biological parameters governing the different outcomes to these therapies. We also propose mechanisms whereby blocking CTLA-4 and PD-1 may be used in combination with other agents to give much better survival in advanced disease ovarian cancer patients. ABSTRACT: This review provides an update on the current use of immune checkpoint inhibitors (ICI) in female gynecologic cancers, and it addresses the potential of these agents to provide therapy options for disease management and long-term remission in advanced disease patients, where surgery, chemotherapy, and/or radiation fail to meet this goal. The topic of immune checkpoint inhibitors (ICI) blocking cytotoxic T lymphocyte associated protein-4 (CTLA-4) and the programmed death-1 (PD-1) axis has come to the forefront of translational medicine over the last decade for several malignancies. The text will focus primarily on a discussion of ovarian cancer, which is the most frequent cause of death of gynecologic cancers; endometrial cancer, which is the most often diagnosed gynecologic cancer; and cervical cancer, which is the third most common female gynecologic malignancy, all of which unfavorably alter the lives of many women. We will address the critical factors that regulate the outcome of these cancer types to ICI therapy, the ongoing clinical trials in this area, as well as the adverse immune responses that impact the outcome of patients given ICI regimens.