Abstract 289: A novel ex-vivo organotypic culture platform for functional interrogation of human appendiceal neoplasms

Abstract Appendiceal neoplasms are rare and often clinically present with peritoneal metastasis. While surgical tumor resection is effective for some types of primary appendiceal cancers, patients with metastatic disease have poor prognostic outcomes. Models to study appendix cancer biology are limited, given that 1) no mouse models exist and 2) reliable in vitro models are unavailable. As such, we have developed an ex-vivo organotypic slice model to examine cellular interactions between tumor cells and their local microenvironment. Tumor specimens from human appendiceal cancer patients were cut using a vibratome to make 200 μm organotypic slices. Slices were cultured on transwell inserts and tested for changes in morphological, cellular and functional characteristics over a seven-day period. Organotypic slices maintained their cellular composition in regard to the proportion of epithelial, immune cells and fibroblasts. Live cell [Ca2+]i imaging of long term cultured slices confirmed that immune cells remain functionally active when stimulated with extracellular ATP. Lasty, using tumor biopsies from human donors, we have identified a diverse immunological profile of appendiceal tumors not previously identified. Our study illustrates a novel approach for studying the pathophysiology of appendiceal cancer, a notoriously difficult disease to model. Citation Format: Jonathan Weitz, Tatiana Hurtado de Mendoza, Herve Tiriac, Joel Baumgartner, Kaitlyn Kelly, Jula Veerapong, Andrew Lowy. A novel ex-vivo organotypic culture platform for functional interrogation of human appendiceal neoplasms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 289.