Predictive biomarkers for immunotherapy response in endometrial cancer: current insights and future directions

In recent years, immunotherapy has modified the treatment landscape of advanced and recurrent endometrial cancer (a/rEC), particularly for patients with defective mismatch repair and microsatellite instability-high (dMMR/MSI-H), significantly improving their outcomes. Its success in later treatment lines has led to its investigation and adoption as a first-line therapy, alone or with chemotherapy. However, despite the high and long-lasting efficacy of immune checkpoint inhibitors (ICIs) in dMMR/MSI-H EC, not all patients benefit from this treatment, and reasons underscoring primary resistance in this setting remain poorly understood and are not yet incorporated into clinical decision-making. Additionally, the correlation between ICI response, tumor mutational burden (TMB), and PD-L1 expression, well-documented in other tumors, appears inconsistent in EC. While proficient mismatch repair and microsatellite stable (MMRp/MSS) EC remain an unmet medical need, some patients within this group still respond to ICIs. Although several biomarkers, including TP53, BRCA, and homologous recombination deficiency (HRD), have been investigated, none have proven to be definitively predictive. This review examines the relevant trials with ICIs as a single agent or in combination in EC and explores the available evidence on potential predictive biomarkers.