Immune landscape and potential role of immune checkpoint inhibitors on uterine leiomyosarcoma: a review

Uterine leiomyosarcoma is a rare and aggressive malignancy with limited therapeutic options and poor prognostic outcomes. Immune checkpoint inhibitors have transformed oncology; however, their efficacy in leiomyosarcoma remains uncertain. This review explores the immunological landscape of uterine leiomyosarcoma, focusing on the role of checkpoint blockade and potential strategies to optimize treatment. The tumor microenvironment plays a crucial role in shaping immune responses, with leiomyosarcomas often exhibiting variable programmed death-ligand 1 expression, differential lymphocytic infiltration, and interactions with tumor-associated macrophages. Despite modest response rates in clinical trials, molecular analyses suggest that specific sub-groups may derive greater benefit from checkpoint inhibition. Moreover, dual-checkpoint blockade combining anti-programmed death-1 and anti-cytotoxic T-lymphocyte-associated antigen-4 agents has demonstrated enhanced immune activation in select patients. In addition, chemotherapy-induced immunogenic cell death has been explored as a complementary approach to immunotherapy. These findings support the need for innovative combinatorial strategies aimed at augmenting immune responsiveness in leiomyosarcoma. The integration of checkpoint inhibitors with targeted immunomodulation and personalized therapeutic approaches may improve treatment efficacy. Future research should focus on refining patient selection criteria, enhancing macrophage-targeted therapies, and optimizing immune profiling techniques to maximize therapeutic outcomes for uterine leiomyosarcoma.