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bioRxiv · 10.1101/2022.09.09.507299

An Immune Cell Recirculation-Enabled Microfluidic Array to Study Dynamic Immunotherapeutic Activity in Recapitulated Tumor Microenvironment

Chi, C.-W.·Lao, Y.-H.·Ahmed, A. H. R.·He, S.·Merghoub, T.·Leong, K. W.·Wang, S.
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Abstract

The efficacy of immunotherapeutic treatment protocols to enable immune cell mediated treatment of cancer is significantly modulated in the presence of tumor microenvironment (TME) which is a key factor in providing both a physical barrier and immunosuppressive stimuli. Herein, we developed a recirculating, high-throughput microfluidic cell array to capture these crucial players - cytotoxic T cells in circulation, endothelium, and tumor stroma. The system consisted of a three-layered cell array spatially emulating TME, with T cell circulation sustained via fluidic recirculating circuits. This allowed us to study the dynamic TME/circulation system and cancer cell response thereof. The system further revealed that tumor endothelium exhibited a hindrance to T cell infiltration into the breast cancer tumor compartment, which was alleviated when treated with anti-human PD-L1 antibody. The other key stromal component, cancer associated fibroblasts, further attenuated T cell infiltration, and led to reduced apoptosis activity in cancer cells. These results confirm the capability of our tumor-on-a-chip system to recapitulate some key immune cell interactions with the reconstructed TME, along with demon-strating as the feasibility of using this system for high-throughput cancer immunotherapeutic screening.

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Chi, C.-W., Lao, Y.-H., Ahmed, A. H. R., He, S., Merghoub, T., Leong, K. W., Wang, S.. 2022-09-12. An Immune Cell Recirculation-Enabled Microfluidic Array to Study Dynamic Immunotherapeutic Activity in Recapitulated Tumor Microenvironment. https://doi.org/10.1101/2022.09.09.507299

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