Abstract
Background/Objectives: Cancer immunotherapy through the use of PD-1/PD-L1 inhibitors have shown significant promise in endometrial carcinoma (EC), particularly in tumors with microsatellite instability (MSI) or mismatch repair deficiency (dMMR), present in approximately 30% of cases. This review evaluated PD-L1 and PD-1 expression as potential biomarkers for immunotherapy response in EC, focusing on their relationship with MSI status. Methods: A systematic review, adhering to PRISMA guidelines, analyzed studies from MEDLINE and Embase until February 2023 on PD-1/PD-L1 expression in EC stratified by MSI status, including diverse study designs but excluding conference abstracts, with independent screening, data extraction, and additional reference checks to ensure comprehensive coverage. Results: A systematic analysis of 10 studies found that PD-L1 expression was more frequently expressed in MSI tumors (49%) compared to microsatellite-stable tumors (MSS) (33.5%), while PD-1 was expressed in 58% of MSI cases and 48% of MSS cases. Despite these findings, the prognostic value of PD-L1/PD-1 remains uncertain, with conflicting results regarding their association with survival outcomes. PD-L1 expression varied across molecular subtypes, being highest in POLE-mutated tumors (76.56%) and serous carcinomas (73%). Differences in PD-L1 expression between primary and metastatic sites were also noted, complicating its use as a biomarker. Conclusions: The assessment of PD-L1 expression in EC could represent a valuable option for selecting patients who may benefit from immune checkpoint inhibitors (ICI), including those in the MSS cohort, thereby ensuring a more tailored and personalized treatment strategy.