The immune microenvironment in endometrial carcinoma: mechanisms and therapeutic targeting

Endometrial carcinoma (EC) represents one of the most prevalent malignancies within the female reproductive system. The frequency of its occurrence is on the rise annually, and patients diagnosed at advanced stages face a less favorable prognosis. Recent studies have highlighted the significant influence of the tumor immune microenvironment (TME) on the initiation, progression, metastasis, and therapeutic resistance of endometrial cancer. The TME encompasses various components such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), immune cells, and the extracellular matrix (ECM). These elements contribute to an immunosuppressive milieu by secreting cytokines, extracellular vesicles (EVs), and engaging immune checkpoint pathways like PD-1/PD-L1, thereby supporting tumor immune evasion and resistance to treatment. This review synthesizes current understanding of the EC-TME, focusing on the distinct roles and interactions of its key constituents within the context of EC biology. Furthermore, we explore the rationale and progress for novel therapeutic strategies targeting the TME, such as immune checkpoint inhibitors, combination therapies, and nano delivery systems leveraging EVs, aiming to provide insights for improving EC patient outcomes.