Patient-derived organoid – immune cell co-culture platform for therapeutics discovery in high-grade endometrial cancer

We established a biobank of 85 patient-derived organoids (PDOs) generated from 44 individuals, encompassing a broad range of endometrial cancer (EC) subtypes, including a majority of high-grade endometrial cancer (HGEC) PDOs from African American patients. From these same patients, we isolated autologous immune cells, enabling the creation of PDO–immune cell co-cultures that reflect each patient's unique characteristics without evoking allogeneic immune responses. To dissect the roles of antigen presentation pathways and evaluate proof-of-principle immunotherapeutic interventions, we performed bulk RNA sequencing, flow cytometry, and live-cell imaging. Overall design: Bulk RNA-seq profiling of endometrial cancer patient-derived organoids (PDOs) and matched normal (CTL).