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Numerous studies are exploring the use of cell adoptive therapies to treat hematological malignancies as well as solid tumors. However, there are numerous factors that dampen the immune response, including viruses like human immunodeficiency virus. In this study, we leverage human-derived microphysiological models to reverse-engineer the HIV-immune system interaction and evaluate the potential of memory-like natural killer cells for HIV⁺head and neck cancer, one of the most common tumors in patients living with human immunodeficiency virus. Here, we evaluate multiple aspects of the memory-like natural killer cell response in human-derived bioengineered environments, including immune cell extravasation, tumor penetration, tumor killing, T cell dependence, virus suppression, and compatibility with retroviral medication. Overall, these results suggest that memory-like natural killer cells are capable of operating without T cell assistance and could simultaneously destroy head and neck cancer cells as well as reduce viral latency.

Breast tumor progression is a complex process involving intricate crosstalk between the primary tumor and its microenvironment. In the context of breast tumor‐lymphatic interactions, it is unclear how breast cancer cells alter the gene expression of lymphatic endothelial cells and how these transcriptional changes potentiate lymphatic dysfunction. Thus, there is a need for in vitro lymphatic vessel models to study these interactions. In this work, a tumor‐lymphatic microfluidic model is developed to study the differential conditioning of lymphatic vessels by estrogen receptor‐positive (i.e., MCF7) and triple‐negative (i.e., MDA‐MB‐231) breast cancer cells. The model consists of a lymphatic endothelial vessel cultured adjacently to either MCF7 or MDA‐MB‐231 cells. Quantitative transcriptional analysis reveals expression changes in genes related to vessel growth, permeability, metabolism, hypoxia, and apoptosis in lymphatic endothelial cells cocultured with breast cancer cells. Interestingly, these changes are different in the MCF7‐lymphatic cocultures as compared to the 231‐lymphatic cocultures. Importantly, these changes in gene expression correlate to functional responses, such as endothelial barrier dysfunction. These results collectively demonstrate the utility of this model for studying breast tumor‐lymphatic crosstalk for multiple breast cancer subtypes.