Title : Planar microorganoPit-based co-culture platform (MICA) for studying tumor-immune interactions in patient-derived tumoroids
Abstract:
Mechanistic studies of tumor-immune interactions and preclinical evaluation of immunotherapies require in vitro models that closely recapitulate the tumor microenvironment. Although patient-derived tumor organoids preserve key structural and functional features of native tumors, existing immune co-culture systems often lack spatial control, scalability, and robust methods to monitor immune-cell infiltration and tumor responses within a physiologically relevant extracellular matrix. Here, we present the MicroOrganoPit Co-culture Assay (MICA), a planar, matrix-based platform for studying immune-tumor interactions in patient-derived tumoroids. Built on patented MicroOrganoPit (MOP) technology developed with ibidi GmbH, MICA stabilizes thin planar hydrogel layers, creating a defined 3D microenvironment that enables the controlled spatial organization of tumoroids and immune cells while remaining fully accessible to high-resolution live-cell microscopy. MICA allows activated lymphocytes to migrate through the collagen matrix and infiltrate tumoroids, thereby inducing tumoroid disruption and enabling direct visualization of infiltration dynamics and immune-mediated cytotoxicity in a single system. In preliminary proof-of-concept experiments, EGFR-targeted CAR T cells showed enhanced infiltration and tumoroid killing compared with control CAR T cells. Overall, MICA provides a scalable, high-throughput, microscopy-compatible, and quantitative platform approach for investigating tumor-immune interactions and evaluating preclinical immunotherapies in patient-derived tumoroids, hereby offering a versatile tool for translational immuno-oncology research.
