3D Microfluidic model for evaluating immunotherapy efficacy by tracking dendritic cell behaviour toward tumor cells

Stefania Parlato, Adele De Ninno, Rosa Molfetta, Elena Toschi, Debora Salerno, Arianna Mencattini, Giulia Romagnoli, Alessandra Fragale, Lorenzo Roccazzello, Maria Buoncervello, Irene Canini, Enrico Bentivegna, Mario Falchi, Francesca Romana Bertani, Annamaria Gerardino, Eugenio Martinelli, Corrado Natale, Rossella Paolini, Luca Businaro, Lucia Gabriele

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Abstract

Immunotherapy efficacy relies on the crosstalk within the tumor microenvironment between cancer and dendritic cells (DCs) resulting in the induction of a potent and effective antitumor response. DCs have the specific role of recognizing cancer cells, taking up tumor antigens (Ags) and then migrating to lymph nodes for Ag (cross)-presentation to naïve T cells. Interferon-α-conditioned DCs (IFN-DCs) exhibit marked phagocytic activity and the special ability of inducing Ag-specific T-cell response. Here, we have developed a novel microfluidic platform recreating tightly interconnected cancer and immune systems with specific 3D environmental properties, for tracking human DC behaviour toward tumor cells. By combining our microfluidic platform with advanced microscopy and a revised cell tracking analysis algorithm, it was possible to evaluate the guided efficient motion of IFN-DCs toward drug-Treated cancer cells and the succeeding phagocytosis events. Overall, this platform allowed the dissection of IFN-DC-cancer cell interactions within 3D tumor spaces, with the discovery of major underlying factors such as CXCR4 involvement and underscored its potential as an innovative tool to assess the efficacy of immunotherapeutic approaches.

Original languageEnglish
Article number1093
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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ASJC Scopus subject areas

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Cite this

Parlato, S., De Ninno, A., Molfetta, R., Toschi, E., Salerno, D., Mencattini, A., Romagnoli, G., Fragale, A., Roccazzello, L., Buoncervello, M., Canini, I., Bentivegna, E., Falchi, M., Bertani, F. R., Gerardino, A., Martinelli, E., Natale, C., Paolini, R., Businaro, L., & Gabriele, L. (2017). 3D Microfluidic model for evaluating immunotherapy efficacy by tracking dendritic cell behaviour toward tumor cells. Scientific Reports, 7(1), [1093]. https://doi.org/10.1038/s41598-017-01013-x