Endometrial cancer is one of the most common gynecological malignancies, and while early-stage cases are highly treatable, recurrent or advanced EC remains challenging to manage. Immunotherapy, particularly immune checkpoint inhibitors, has revolutionized treatment approaches in oncology, and its application in EC has shown promising results. Key to immunotherapy efficacy in EC is the tumor’s mismatch repair status, with MMR-deficient tumors demonstrating a higher tumor mutational burden and increased PD-L1 expression, making them more susceptible to immune checkpoint inhibitors (ICIs) such as pembrolizumab, durvalumab, and dostarlimab. However, not all mismatch repair-deficient (MMRd) tumors respond to ICIs, particularly those with a “cold” tumor microenvironment (TME) characterized by poor immune infiltration. In contrast, some MMR-proficient tumors with a “hot” TME respond well to ICIs, underscoring the complex interplay between MMR status, tumor mutational burden (TMB), and TME. To overcome resistance in cold tumors, novel therapies, including Chimeric Antigen Receptor (CAR) T cells and tumor-infiltrating lymphocytes are being explored, offering targeted immune-based strategies to enhance treatment efficacy. This review discusses the current understanding of immunotherapy in EC, emphasizing the prognostic and therapeutic implications of MMR status, TME composition, and emerging cell-based therapies.

Endometrial cancer, the most prevalent gynecological malignancy in developed countries, is experiencing a sustained rise in both its incidence and mortality rates, primarily attributed to extended life expectancy and lifestyle factors. Currently, the absence of precise diagnostic tools hampers the effective management of the expanding population of women at risk of developing this disease. Furthermore, patients diagnosed with endometrial cancer require precise risk stratification to align with optimal treatment planning. Metabolomics technology offers a unique insight into the molecular landscape of endometrial cancer, providing a promising approach to address these unmet needs. This comprehensive literature review initiates with an overview of metabolomic technologies and their intrinsic workflow components, aiming to establish a fundamental understanding for the readers. Subsequently, a detailed exploration of the existing body of research is undertaken with the objective of identifying metabolite biomarkers capable of enhancing current strategies for endometrial cancer diagnosis, prognosis, and recurrence monitoring. Metabolomics holds vast potential to revolutionize the management of endometrial cancer by providing accuracy and valuable insights into crucial aspects.