Abstract 1151: A unique layered 3D stromal tissue model for in vitro evaluation of immunologic agents and immune cell infiltration into cancer microenvironment

Abstract

Abstract Background; The modulation of the immune system is a proven key target for cancer therapy, however, the complex interplay between immune cells and cancer cells in cancer microenvironment remains only partially understood. In addition, the currently available in vitro cancer microenvironment models are not designed to study the immunologic agents and a role of immune cells. Here, we developed a unique layered 3D stromal tissue model comprising an allogeneic immune, stromal and cancer cells. Method; Human umbilical vein endothelial cells (HUVEC) and normal human dermal fibroblasts (NHDF) were coated with collagen and heparin to construct Extracellular matrix (ECM) nanofilm and cultured to form multi-layers. Lung cancer cells were placed between stromal cells. Furthermore, we added Peripheral Blood Mononuclear Cell (PBMC) and Programmed cell death 1 (PD-1) blockade with Nivolumab and evaluated cytotoxic effects of immune cells on cancer cells and immune cell infiltration by immunohistochemistry. Result; The co-cultured stromal tissues were multi-layered (approximately 20 layers), and the presence of lung cancer cells between stromal cells was observed. Immunohistochemistry revealed CD8 positive immune cell infiltration into the fibroblast layers. PBMC with Nivolumab treatment significantly decreased the viability of lung cancer cells in this 3D co-culture compared with the results in 2D mono-culture. High level of programmed cell death ligand 1 (PD-L1) expression on lung cancer cell lines correlated with a higher response to PD-1 blockade in vitro as well as clinical trials. Conclusion; In summary, we present a unique 3D cell culture system based on an allogeneic stromal/cancer/immune cell setting to study immunologic agents and immune cell infiltration in cancer microenvironment. This 3D model has the ability to reflect in vivo conditions closer than 2D model and provide a tool for in vitro immunologic agent testing. Citation Format: Rii Morimura, Kei Tsukamoto, Shiro Kitano, Eiji Shinozaki. A unique layered 3D stromal tissue model for in vitro evaluation of immunologic agents and immune cell infiltration into cancer microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1151.