Abstract 1153: Development and validation of a novel in vitro model of the tumor immune microenvironment

Abstract

Abstract Tumor-associated lymphatics and their connection to the tumor-draining lymph node (TDLN) play important roles in cancer metastasis as well as in modulating the immune microenvironment. They bathe the TDLN in cytokines, exosomes, antigens, and suppressive factors from the tumor microenvironment to alter the anti-tumor immune response. These interactions are difficult to study in vivo, yet currently, these interactions cannot be readily explored in vitro. Here, we developed a perfused paper-based cell culture platform which can recreate the 3-dimensional architecture, stromal component and physiological levels of interstitial flow of the native tissue environment, while keeping the device high-throughput, easy to use, and inexpensive. This platform can sustain the long-term cultures (>3 weeks) of a number of tumor cell lines, which form complex architectures reminiscent of actual tumors, as well as of excised tumor tissue. The platform also supports the function and viability of immune cells (such as T lymphocytes and dendritic cells) and stromal cells (such as lymphatic endothelial cells and fibroblasts). To model the tumor interaction with its TDLN, we created a model in which tumor cells and lymph node stromal cells (LNSC) are cultured in separate but connected compartments under perfusion. To validate this, we have demonstrated preferential tumor migration to preconditioned (vs. unconditioned) LN stroma. The LN stroma compartment also supports co-culture of dendritic cells and T lymphocytes. To validate the modeling of the crosstalk between the tumor and TDLN, we show that tumor conditionioning of the LN primes the LN microenvironment to dampen cytotoxic T cell function. Together, these data highlight the potential of this system for studying complex tumor-host cell interactions in the tumor microenvironment over long periods of time, and paves the way towards an in vitro screening platform for drug screening for drugs that target cells or factors in the tumor microenvironment that serve as barriers to both chemotherapy as well as immunotherapies. Citation Format: RUOLAN ZHOU, Rachel Weathered, Luis Alonzo, Renata Mezyk-Kopec, Melody Swartz. Development and validation of a novel in vitro model of the tumor immune 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 1153.