Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model
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fimmu-09-00416.pdf
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Checksum (MD5)
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Author(s)
Lee, Sharon Wei Ling
Adriani, Giulia
Ceccarello, Erica
Pavesi, Andrea
Tan, Anthony Tanoto
Bertoletti, Antonio
Kamm, Roger Dale
Wong, Siew Cheng
Date Issued
March 2018
Journal
Frontiers in Immunology
Publisher
Frontiers Research Foundation
Citation
Lee, Sharon Wei Ling, et al. “Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model.” Frontiers in Immunology, vol. 9, Mar. 2018. © 2018 Lee, Adriani, Ceccarello, Pavesi, Tan, Bertoletti, Kamm and Wong.
Version
Final published version
Abstract
In the hepatitis B virus (HBV)-related hepatocellular carcinoma tumor microenvironment (TME), monocytes reportedly impede natural T cell functions via PD-L1/PD-1 signaling. However, it remains unclear if T cell receptor-redirected T cells (TCR T cells) are similarly inhibited. Hence, we developed a 3D intrahepatic TME microfluidic model to investigate the immunosuppressive potential of monocytes toward HBV-specific TCR T cells and the role of PD-L1/PD-1 signaling. Interestingly, in our 3D static microfluidic model, we observed that monocytes suppressed only retrovirally transduced (Tdx) TCR T cell cytotoxicity toward cancer cells via PD-L1/PD-1, while mRNA electroporated (EP) TCR T cell cytotoxicity was not affected by the presence of monocytes. Importantly, when co-cultured in 2D, both Tdx and EP TCR T cell cytotoxicity toward cancer cells were not suppressed by monocytes, suggesting our 3D model as a superior tool compared to standard 2D assays for predicting TCR T cell efficacy in a preclinical setting, which can thus be used to improve current immunotherapy strategies.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Singapore-MIT Alliance in Research and Technology (SMART)
Terms of Use
Attribution 4.0 International (CC BY 4.0)
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.3389/fimmu.2018.00416
