Introduction/Background Endometrial cancer (EC) is one of the most common female cancers with increasing incidence and disease-associated mortality, worldwide. Recent clinical trials proved the rationale of immune checkpoint inhibitors (ICI) therapies in advanced disease.
Methodology We evaluated the level of RNA expression of immune checkpoints genes programmed cell death 1 (PD1), its ligand (PDL1) and interferon gamma (IFNG) in 239 EC tissues. We had a control group of 25 non-malignant tissues. We performed association and survival analyses. In a cohort of 81 patients we analyzed them according to the PROMISE molecular classification (POLE-mutated, MMRd, p53abn and NSMP).
Results In EC we found significantly higher levels of PD1 (7-fold), PDL1 (3-fold) and IFNG (5-fold) (p<0.001) and these markers were associated with high tumor grade (p =0.007, =0.020, =0.001 respectively). All these immune checkpoint molecules were significantly associated with higher grading of EC. High expression of PD1, PDL1 and IFNG was associated with better recurrence free survival (RFS; HR 0.318, p<0.001; HR 0.295, p<0.001; HR 0.474, p=0.012, respectively) and overall survival (OS; HR 0.563, p=0.003; HR 0.381, p<0.001; HR 0.577, p=0.006; respectively). PD1 was predictive for RFS (HR 0.39, p=0.009) and PDL1 for OS (HR 0.55, p=0.037). POLE mutated and MMRd tumors - so called ’immunological hot tumors’ - showed the highest expression of PD-1 and IFNG.
Conclusion Immune checkpoint molecules are strongly associated with clinical outcomes in patients with EC and their expression should guide therapeutic approaches.
Disclosures No disclosures
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