Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model
Author(s)
Lee, Sharon Wei Ling; Adriani, Giulia; Ceccarello, Erica; Pavesi, Andrea; Tan, Anthony Tanoto; Bertoletti, Antonio; Kamm, Roger Dale; Wong, Siew Cheng; ... Show more Show less
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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.
Date issued
2018-03Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Mechanical Engineering; Singapore-MIT Alliance in Research and Technology (SMART)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
ISSN
1664-3224