IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER

Endometrial carcinoma (EC) represents the most common gynecological malignancy in developed countries. Despite therapeutic advances, patients with advanced or recurrent disease still have a poor prognosis, with high recurrence rates and a 5-year survival of less than 20%. Recently, four phase III studies (RUBY, NRG-GY018, AtTEnd, and DUO-E) have demonstrated that the addition of anti-PD-1/PD-L1 immunotherapy to first-line chemotherapy significantly improves progression-free survival, particularly in tumors with altered DNA repair mechanisms known as mismatch repair (MMR) (so-called mismatch repair-deficient or dMMR tumors), but with benefits also observed in a subset of tumors with normal MMR function (so-called MMR-proficient or pMMR tumors). However, despite the clinical approval of these therapies, reliable biomarkers capable of predicting response to immunotherapy are still lacking. This project aims to comprehensively characterize the genomic, epigenetic, and lipid properties of the tumor and the tumor microenvironment (TME) in order to identify predictive markers of response to immunotherapy, thereby laying the foundation for a personalized therapeutic approach in endometrial carcinoma.

Sex

Female

Minimum age

18 Years

Maximum age

120 Years

Inclusion Criteria:

* Female patients ≥ 18 years old.
* Histologically confirmed epithelial endometrial carcinoma (endometrioid, serous, clear cell, mixed, or carcinosarcoma).
* Advanced (stage III-IV) or recurrent disease, eligible for surgery or biopsy as part of the therapeutic plan.
* Availability of fresh-frozen or OCT-embedded tumor tissue obtained at surgery/biopsy and stored in the IEO Biobank.
* Mismatch-repair-deficient (dMMR) or -proficient (pMMR) molecular subtype (when available).
* Written informed consent for participation and use of biological material for translational research purposes.

Exclusion Criteria:

* Mesenchymal tumors or epithelial tumors of non-endometrial origin (e.g., ovarian, cervical).
* Prior systemic treatment with immune checkpoint inhibitors for other malignancies.
* Insufficient or poor-quality tumor tissue available for molecular analyses.
* Active or uncontrolled infection with HIV, HBV, or HCV.
* Any condition that, in the investigator's judgment, would compromise patient safety or study integrity.