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Title: Characterizing the role of monocytes in T cell cancer immunotherapy using a 3d microfluidic model
Authors: Lee, S.W 
Adriani, G
Ceccarello, E
Pavesi, A
Tan, A.T 
Bertoletti, A 
Kamm, R.D
Wong, S.C 
Keywords: programmed death 1 receptor
T lymphocyte receptor
cancer immunotherapy
CD8+ T lymphocyte
cell aggregation
cell culture
cell expansion
cell interaction
cell isolation
controlled study
cytotoxic T lymphocyte
cytotoxicity assay
flow cytometry
human cell
immunosuppressive treatment
microfluidic analysis
peripheral blood mononuclear cell
protein expression
signal transduction
T lymphocyte activation
Issue Date: 2018
Citation: Lee, S.W, Adriani, G, Ceccarello, E, Pavesi, A, Tan, A.T, Bertoletti, A, Kamm, R.D, Wong, S.C (2018). Characterizing the role of monocytes in T cell cancer immunotherapy using a 3d microfluidic model. Frontiers in Immunology 9 (MAR) : 416. ScholarBank@NUS Repository.
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. © 2018 Lee, Adriani, Ceccarello, Pavesi, Tan, Bertoletti, Kamm and Wong.
Source Title: Frontiers in Immunology
ISSN: 16643224
DOI: 10.3389/fimmu.2018.00416
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