Abstract A107: Microfluidics and oncoimmunology: New in vitro models to study solid tumor immunotherapy

Abstract

Abstract Immunotherapies against solid tumors face daunting challenges compared with hematologic cancers. In solid tumors, immune cells and antibodies need to extravasate from the vasculature, find the tumor cells, and migrate through a dense mass of normal and tumor cells where nutrients are depleted and waste products build up. All these factors pose significant obstacles for solid tumor immunotherapy, commonly leading to immune exhaustion and compromising the immune response. Thus, finding effective immunotherapies against solid tumors requires in vitro models that accurately capture the tumor complexity. In this work, we present microfluidic models for solid tumor immunotherapy and show how they mimic the tumor architecture in an unprecedented way compared with other traditional in vitro models based on Petri dishes. Breast cancer cells were cultured as a dense mass and embedded in a 3D collagen hydrogel into a microfluidic device. Endothelial cells were cultured in lateral flanking lumens to mimic the blood vessels, allowing the perfusion of therapeutic antibodies or effector immune cells (e.g., natural killer cells). Antibody and immune cell extravasation, diffusion, migration, and tumor clearance were evaluated in the model, showing the NK cell capacity to detect the presence of the tumor hundreds of microns away. Once inside the tumor mass, real-time microscopy revealed natural killer cells were able to destroy tumor cells at the tumor periphery and, more importantly, also at the innermost layers. The combination of antibodies and natural killer cells led to an enhanced cytotoxicity, showing the potential of the model to evaluate new immunotherapy combinations. Finally, tumor, endothelial, and NK cells were retrieved at different locations of the tumor (e.g., tumor margin vs. tumor core) and at different time points to show how these different cell populations adapted to the continuously evolving tumor microenvironment. Citation Format: Jose M. Ayuso, Maria Virumbrales-Munoz, Patrick H. McMinn, Shujah Rehman, Cate M. Fitzgerald, David J. Beebe, Melissa C. Skala. Microfluidics and oncoimmunology: New in vitro models to study solid tumor immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A107.