Maureiq Ojwang', Moffitt Cancer Center
Authors: Maureiq Ojwang', Anjun Hu, McKenzie Williams, Sarah Bazargan, Shari Pilon-Thomas, Katarzyna A. Rejniak
2023 AWM Research Symposium
Multiscale modeling for preclinical and clinical oncology [Organized by Maureiq Ojwang' and Chengyue Wu]

Hypoxia is a common feature of solid tumors such as bladder cancers. Mathematical models defined on a cellular level (microscale) of oxygen transport can be used to recreate tissue hypoxia. We designed a hybrid multicell lattice-free agent-based model using continuous oxygen kinetics and discrete cells and vasculature obtained from digitized histology images, to simulate tissue oxygenation. We analyzed bladder cancer tissues obtained from mice that received intravesical treatments of Gemcitabine and/or intravesical adoptive cell therapy with OT-I transgenic CD8+ T cells, in addition to untreated controls. We determined the oxygenation levels, spatial distributions, and colocalizations of immune and tumor cells in untreated vs. treated tissues. Our reconstructed tissue oxygenation based on histology images revealed that hypoxic niches hinder immune cell accumulation in both treated and untreated tumors. Although tumors have hypoxic areas, most of the immune cells were residing in well-oxygenated regions. Such quantitative analyses may encourage designing more effective immunotherapies suited for hypoxic conditions.

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