Tumor Immune Microenvironment in Gynecologic Cancers

SIMPLE SUMMARY: Gynecologic cancers represent a broad spectrum of diseases within the female genital tract. In recent years, the tumor microenvironment has become an active area of investigation leading to the development of novel therapeutics targeting the immune system and shifts in traditional treatment paradigms for gynecologic malignancies. In this review, we delineate what is known currently regarding the tumor immune microenvironment (TIME) in ovarian, endometrial, cervical, and vaginal/vulvar cancers. Additionally, we will review clinical trial data to demonstrate how we are leveraging what we know about the TIME to treat gynecologic malignancies. ABSTRACT: Gynecologic cancers have varying response rates to immunotherapy due to the heterogeneity of each cancer’s molecular biology and features of the tumor immune microenvironment (TIME). This article reviews key features of the TIME and its role in the pathophysiology and treatment of ovarian, endometrial, cervical, vulvar, and vaginal cancer. Knowledge of the role of the TIME in gynecologic cancers has been rapidly developing with a large body of preclinical studies demonstrating an intricate yet dichotomous role that the immune system plays in either supporting the growth of cancer or opposing it and facilitating effective treatment. Many targets and therapeutics have been identified including cytokines, antibodies, small molecules, vaccines, adoptive cell therapy, and bacterial-based therapies but most efforts in gynecologic cancers to utilize them have not been effective. However, with the development of immune checkpoint inhibitors, we have started to see the rapid and successful employment of therapeutics in cervical and endometrial cancer. There remain many challenges in utilizing the TIME, particularly in ovarian cancer, and further studies are needed to identify and validate efficacious therapeutics.