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Front Immunol. 2018 Mar 6;9:416. doi: 10.3389/fimmu.2018.00416. eCollection 2018.

Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model.

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BioSystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore.
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Singapore Immunology Network (SIgN), Biomedical Sciences Institute, Agency for Science, Technology, and Research, Singapore, Singapore.
Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research, Singapore, Singapore.
Programme of Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States.


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.


PD-L1; T cell receptor-redirected T cells; immune checkpoint; immunotherapy; microfluidics; monocytes; tumor microenvironment

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