Abstract 1621: Comparison and consequences of different implantation techniques on the orthotopic growth of syngeneic Hepa1-6 liver cancer cells

Abstract Checkpoint inhibitor treatment has become a common therapy of various cancer types. Still, there is a need for well-characterized preclinical mouse models, as clinical data indicates that patients only partially respond to immune modulatory regiments. When compared to the classical subcutaneous or subQperior࣪ (implantation into the mammary fat pad) syngeneic mouse models, orthotopic models are considered more predictive, since implantation of tumor cells into the organ of origin allows organotypical interaction between tumor cells and the surrounding stroma, including immune cells. Up until now, our standard procedure for an orthotopic Hepa1-6 liver model is the injection of Hepa1-6 cells into the spleen with the subsequent migration of the injected Hepa1 6 cells into the liver for five minutes via Vena lienalis. A major drawback of this method for a syngeneic model in immune-competent mice is the following resection of the spleen, a prominent secondary lymphoid organ. Therefore, we tested two other implantation methods: the direct injection of Hepa1-6 cells into a liver lobe using Matrigel࣪ and the injection of Hepa1-6 cells into the portal vein. In contrast to the standard procedure, both new test methods have in common an excessive bleeding potential which must be prevented. As the Hepa1-6 cells are transduced with luciferase, their growth can be monitored in vivo by bioluminescence imaging and the growth characteristics will be compared. In addition to the growth, the composition of the immune populations will be analyzed staining with the all-in-one flow cytometry panel which permits the differentiation of the main immune cell populations in the tumor, such as T cells (CD4+, CD8+, Treg), B and NK cells, macrophages (M1/M2), MDSCs (granulocytic and monocytic), and dendritic cells. The data will help to select the most suitable method for testing new drug candidates in an orthotopic liver tumor environment. Citation Format: Cynthia Obodozie, Sandra Moor, Gojko Bijelic, Muriel Malaisé, Philipp Metzger, Holger Weber. Comparison and consequences of different implantation techniques on the orthotopic growth of syngeneic Hepa1-6 liver cancer cells [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 1621.