Impact of Altered Oxygen Level on the Growth Dynamics of Hanging Tumor

Alex Saul Salas-Tlapaya, Anabel Sánchez-Sánchez, Raquel Díaz-Hernández, Leopoldo Altamirano-Robles

Abstract


Cancer immunotherapy approaches arebased on the interaction between cancer cells (CC) andimmune cells in a microenvironment that determines the survival of one or the other cell type. Within this context, macrophages play a critical role, as they candirectly destroy CCs by processes such as phagocytosis. Additionally, hypoxia in the tumor microenvironment is crucial, as altered oxygen levels can induce CC necrosis. Performing these studies in vitro presents temporal limitations, high lighting the relevance of computational simulations. This study explores how variations in oxygen levels affect tumor growth in an immunotherapy model using the PhysiCell simulation environment. We systematically modified oxygen (02) levels and observed their impact on CC proliferation over 25 days. The results reveal distinctive growth patterns: model y1 showed an initial progressive growth until day 13, followed by a marked decrease due to the activation of immune responses with a medium oxygen level. Model y2, with a 2 % increase in oxygen, exhibited more rapid and sustained growth, indicating increased tumor resistance. The model y3, with a 1% decreasein oxygen, also showed an increase in tumor growth but with distinct peaks at approximately day 14. The correlation coefficients between y1 and y2 (0.926), y1 and y3 (0.921), and finally, y2 and y3 (0.994) support the consistency and interdependence between the models, suggesting that modifications in one factor will similarly affect the other models. This study underscores the importance of oxygen in tumor growth dynamics and how its manipulation may be key to developing more effective immunotherapy strategies for cancer treatment, saving valuable time through computational simulations.

Keywords


Immunotherapy, simulation, hypoxia, cancer, macrophages

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