Short-term culture of human endoscopic specimens for the study of chronic inflammation

Inflammation and cell death are central to both chronic inflammatory disorders and cancer progression, influencing tissue homeostasis, therapeutic response, and resistance. Effective preclinical models that preserve the human microenvironment are required to study these processes, guide personalized therapy or to test pharmacologically active substances. We developed patient-derived tissue slice cultures from endoscopic specimens (ePDTC) such as gastrointestinal and pulmonary cancers, as well as inflamed mucosa from patients with Inflammatory bowel disease (IBD). These tissue cultures preserve epithelial, stromal, and immune compartments, enabling analysis of inflammatory signalling and cell death pathways while allowing parallel pharmacological testing. PDTCs maintained tissue cytoarchitecture and cell-cell interactions, permitting within-patient drug response profiling and capturing inter- and intra-patient heterogeneity. This enabled mechanistic investigation of inflammation-driven resistance and individualized assessment of chemotherapies, immunotherapies, and anti-inflammatory agents. Here, we describe a protocol for establishing ePDTC from diverse anatomical sites to provide a translational platform to study immune regulation and therapy response in human cancers and inflammatory diseases, supporting development of personalized treatment strategies.