Molecular Characterizations of Gynecologic Carcinosarcomas: A Focus on the Immune Microenvironment

SIMPLE SUMMARY: Gynecologic carcinosarcomas are rare and highly aggressive tumors. Despite treatment, response rates are low, and the survival outcomes of patients with carcinosarcoma are far worse than high-grade tumors of the same origin. Due to this, there is a need for new, tailored therapies. The role of immunotherapy has not been extensively studied in gynecologic carcinosarcomas, but emerging studies suggest that there is a potential role that should be explored further. The aim of this review is to outline the current knowledge about gynecologic carcinosarcomas, with a focus on their molecular profiles and the tumor immune microenvironment, and discuss possible directions for future research. ABSTRACT: Gynecologic carcinosarcomas, specifically of endometrial and ovarian origin, are aggressive and rare tumors. Treatment data are limited and are often extrapolated from other histologies and smaller retrospective studies. While the optimal therapy approach remains contentious, treatment is often multimodal and may include surgery, chemotherapy, radiation, or a combination of multiple strategies. However, despite aggressive treatment, these tumors fare worse than carcinomas of the same anatomic sites irrespective of their stage. Recent studies have described in-depth molecular characterizations of gynecologic carcinosarcomas. Although many molecular features mirror those seen in other uterine and ovarian epithelial tumors, the high prevalence of epithelial-mesenchymal transition is more unique. Recently, molecular descriptions have expanded to begin to characterize the tumor immune microenvironment. While the importance of the immune microenvironment has been well-established for other tumor types, it has been less systematically explored in gynecologic carcinosarcomas. Furthermore, the use of immunotherapy in patients with gynecologic carcinosarcomas has not been extensively evaluated. In this review, we summarize the available data surrounding gynecologic carcinosarcomas, with a focus on the immune microenvironment. We end with a discussion of potential immunotherapy uses and future directions for the field.