Microphysiological model reveals the promise of memory-like natural killer cell immunotherapy for HIV± cancer

Jose M. Ayuso (), Mehtab Farooqui, María Virumbrales-Muñoz, Katheryn Denecke, Shujah Rehman, Rebecca Schmitz, Jorge F. Guerrero, Cristina Sanchez- de-Diego, Sara Abizanda Campo, Elizabeth M. Maly, Matthew H. Forsberg, Sheena C. Kerr, Robert Striker, Nathan M. Sherer, Paul M. Harari, Christian M. Capitini, Melissa C. Skala and David J. Beebe
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Jose M. Ayuso: University of Wisconsin School of Medicine and Public Health
Mehtab Farooqui: University of Wisconsin School of Medicine and Public Health
María Virumbrales-Muñoz: University of Wisconsin School of Medicine and Public Health
Katheryn Denecke: University of Wisconsin School of Medicine and Public Health
Shujah Rehman: Morgridge Institute for Research
Rebecca Schmitz: University of Wisconsin
Jorge F. Guerrero: University of Wisconsin
Cristina Sanchez- de-Diego: University of Wisconsin School of Medicine and Public Health
Sara Abizanda Campo: University of Wisconsin School of Medicine and Public Health
Elizabeth M. Maly: University of Wisconsin
Matthew H. Forsberg: University of Wisconsin School of Medicine and Public Health
Sheena C. Kerr: University of Wisconsin School of Medicine and Public Health
Robert Striker: University of Wisconsin School of Medicine and Public Health
Nathan M. Sherer: University of Wisconsin
Paul M. Harari: University of Wisconsin School of Medicine and Public Health
Christian M. Capitini: University of Wisconsin
Melissa C. Skala: University of Wisconsin
David J. Beebe: University of Wisconsin School of Medicine and Public Health

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-41625-8

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