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Microfluidic Co-Culture Models for Dissecting the Immune Response in in vitro Tumor Microenvironments
Published on: April 30, 2021
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Enabling continuous immune cell recirculation on a microfluidic array to study immunotherapeutic interactions in a
Chun-Wei Chi1,2, Yeh-Hsing Lao2,3, A H Rezwanuddin Ahmed1
1Department of Biomedical Engineering, CUNY - City College of New York, New York, NY, 10031, USA. shwang@ccny.cuny.edu.
Lab on a Chip
|January 5, 2024
Summary
A novel microfluidic chip recreates the tumor microenvironment (TME) to study immune cell interactions. This system identified tumor endothelium and fibroblasts as barriers to T cell infiltration, highlighting potential immunotherapy targets.
Area of Science:
- Biomedical Engineering
- Cancer Immunology
- Microfluidics
Background:
- The tumor microenvironment (TME) significantly impacts immunotherapy efficacy by modulating immune cell interactions.
- Endothelium and tumor stroma within the TME present physical and immunosuppressive barriers to anti-cancer immune responses.
Purpose of the Study:
- To develop a recirculating microfluidic chip system that spatially reconstructs the TME.
- To investigate the dynamic interactions between immune cells, tumor cells, and stromal components within a simulated TME.
- To identify key barriers to T cell infiltration and evaluate potential therapeutic interventions.
Main Methods:
- Development of a three-layered microfluidic cell array (μFCA) emulating the TME.
- Implementation of tailored fluidic circuits for continuous T cell recirculation.
- Assessment of T cell infiltration and cancer cell apoptosis in response to TME components and anti-human PD-L1 antibody treatment.
Main Results:
- Tumor endothelium was observed to significantly hinder T cell infiltration into the reconstructed tumor compartment.
- Treatment with anti-human PD-L1 antibody demonstrated an ability to alleviate the inhibitory effect of tumor endothelium.
- Cancer-associated fibroblasts attenuated T cell infiltration more than normal fibroblasts, leading to reduced cancer cell apoptosis.
Conclusions:
- The developed tumor-on-a-chip system effectively recapitulates TME complexity to identify immunotherapy targets.
- The findings highlight tumor endothelium and cancer-associated fibroblasts as critical barriers to effective T cell-mediated anti-cancer immunity.
- This platform shows promise for high-throughput screening of cancer immunotherapeutics and overcoming immunotherapy resistance.
