Abstract A037: Mathematical modeling of the tumor-immune microenvironment in murine colon adenocarcinoma

Abstract

Abstract Colon cancer is currently the fourth most common cancer in the United States, impacting over 100,000 people every year with increasingly younger patients affected by the malignancy. As a result, it is imperative to better understand the mechanisms that are involved in the development of colon cancer within the body. The intestine houses the largest compartment of the human body’s immune system, and the intestinal immune system has been implicated in the development of disease and malignancy of both the colon itself and other organ systems throughout the body. In particular, the colon contains high numbers of IgA antibodies (produced by B-cells) in conjunction with regulatory T cells (Treg). Because of the colon’s rich immune system involvement, we are interested in recapitulating several of the immune components and their roles in both targeting tumors and aiding tumors in their aggression. We strive to develop an accurate model of anti-tumor immune cells (CD8+ T-cells, CD4+ T-cells, Natural Killer Cells, Macrophages, Dendritic Cells, Neutrophils) and immunosuppressive cells (Treg, Myeloid-Derived Suppressor Cells) and their engagement with colon adenocarcinoma. The model is built in a nested fashion, beginning with the parametrization of a model of a monolayer from cell cycle and doubling time data. Growth parameters are subsequently obtained for spheroids with no immune cells, spheroids with immune cells, allograft studies in immunocompromised mice, and allograft studies in mice with intact immune systems. The model further incorporates cell cycle stages, quiescence, necrosis, VEGF and TNF-alpha production, and vascularization of the in vivo tumors. The data used to parametrize our model is obtained from literature centered around experiments with CT26 BALB/c murine colon adenocarcinoma both in vitro and in vivo. This cell line is of particular interest because of the large body of publications that utilize it and because the cells form tumors in both immunocompromised and syngeneic BALB/c mice thereby allowing for parametrization of the in vivo model both with and without immune interaction. There are additionally experimental studies through which spheroids were generated with various immune cell infiltrates, thereby enabling more accurate parametrization of each of the immune populations and their impacts on tumor development. We thus aim to develop a novel ODE model of colon adenocarcinoma and the various immune cells that engage in the tumor microenvironment to better evaluate the impacts of these immune populations and the outcomes of immunotherapy targeted at these cells. Citation Format: Frederika Rentzeperis, Maya Srinivasan, Dorothy Wallace. Mathematical modeling of the tumor-immune microenvironment in murine colon adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A037.