In recent years, the introduction of immune checkpoint inhibitors (ICI) in combination with chemotherapy has significantly changed the management of advanced and recurrent Endometrial Cancer (EC).

Despite these advances, responses to immunotherapy remain heterogeneous. Not all patients with mismatch repair-deficient (dMMR) tumors derive durable benefit, while a subset of mismatch repair-proficient (pMMR) tumors may respond. In addition, ICI treatment is associated with relevant costs and immune-related toxicities, highlighting the need for improved patient selection. To date, no validated predictive biomarkers beyond mismatch repair (MMR) status are available, reflecting limited understanding of the biological mechanisms underlying sensitivity and resistance to immunotherapy in EC.

This study aims to assess and integrate molecular and epigenetic features to identify prognostic and predictive biomarkers of immunotherapy response in endometrial cancer, and to explore their functional relevance using patient-derived experimental models.

Inclusion Criteria:

• Age ≥ 18 years
• Histologically confirmed advanced or recurrent endometrial carcinoma or carcinosarcoma
• No prior treatment with immune checkpoint inhibitors
• Availability of paired fresh-frozen and FFPE tumor samples
• Provision of written informed consent for participation in translational research

Exclusion Criteria:

• Refusal or inability to provide informed consent by the patient or legal representative
• Mesenchymal tumors or epithelial tumors of non-endometrial origin (e.g., ovarian cancer)
• Active treatment with immunomodulatory agents at the time of sample collection (e.g., immunotherapy for autoimmune disease)
• Known positivity for HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)