20.500.12556/DiRROS-29419 Soluble immune checkpoints in endometrial cancer - a discovery study Background: Soluble immune checkpoints (sICs) are circulating forms of membrane-bound immune molecules, the latter being targets of immune checkpoint inhibitors, widely used in cancer treatment. Altered sIC levels have been reported in several malignancies and sICs are posited as promising diagnostic, prognostic and predictive biomarkers measurable in peripheral blood. However, data on their levels in endometrial cancer (EC) patients are scarce. This study aimed to evaluate plasma concentrations of multiple sICs in EC patients and assess their potential diagnostic, prognostic, and predictive value. Methods: In this prospective case-control study, plasma levels of 16 soluble immune checkpoints were measured in 50 patients with histologically confirmed EC prior to surgical staging and in 26 age- and BMI-matched controls undergoing benign gynecologic surgery. Fluorescence-based multiplex immunoassay (MagPix, Luminex) was used to quantify analyte concentrations. FIGO 2023 stage classification and risk grouping according to ESGO 2020 guidelines was performed based on clinicopathologic data and molecular characteristics (MMR and p53 status). Statistical analyses were performed using non-parametric tests and robust logistic regression. Results: EC and control groups did not differ in demographic, clinical, or lifestyle parameters. sIC levels were measurable in majority of patients. No significant differences in sIC levels were observed between EC patients and controls. Within the EC cohort, patients with MMR-deficient tumors exhibited significantly elevated levels of sPD-1, sPD-L1, sLAG-3, sICOS, sGITR, and sCD86 compared with MMR-proficient cases. Higher plasma concentrations of sTIM-3, sCD27, sHVEM, and sCD40 were associated with the presence of lymphovascular space invasion (LVSI). Levels of sCD27 and sCD40 were significantly higher in advanced or metastatic disease (stage IIIA or higher). Conclusions: Although soluble immune checkpoint levels did not differentiate EC patients from controls, several sICs correlated with key prognostic and predictive features, including LVSI, advanced stage, and MMR deficiency. These findings suggest that circulating immune checkpoint proteins may serve as non-invasive biomarkers for risk assessment and immunotherapy response prediction in endometrial cancer. Further validation in larger, independent cohorts is warranted. diagnosticbiomarker endometrial cancer immune checkpoint inhibitor lymphovascular spaceinvasion mismatch repair deficiency predictive biomarker prognostic biomarker soluble immune checkpoint diagnostični biomarker rak endometrija zaviralec imunske kontrolne točke invazija limfovaskularnega prostora pomanjkanje popravljanja neusklajenosti napovedni biomarker prognostični biomarker topna imunska kontrolna točka true false true Angleški jezik Slovenski jezik Neznano 2026-05-18 12:08:58 2026-05-18 12:08:59 2026-05-19 03:54:40 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 10. 12. 2025; str. 1-12 iss. [article no.] 1721822 Vol. 16 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 618.1:577.2 1664-3224 10.3389/fimmu.2025.1721822 260862467 RAZ_Pirs_Bostjan_2025.pdf RAZ_Pirs_Bostjan_2025.pdf 1 113FB99BF4C46D08D9BBA2094F3D75D8 c721aa9fdeb2bd2bdfef520e13ad50be8fd1cebb16279f73f5a8fb30b020dc05 bb6a00c4-52a1-11f1-8a5a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44106 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1721822/full 1 975fa957-52a1-11f1-8a5a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44105 Univerzitetni klinični center Ljubljana 0 0 0