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https://doi.org/10.3389/fimmu.2018.00416
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 Article cancer immunotherapy CD8+ T lymphocyte cell aggregation cell culture cell expansion cell interaction cell isolation controlled study cytotoxic T lymphocyte cytotoxicity assay electroporation flow cytometry human human cell immunosuppressive treatment impedance microfluidic analysis monocyte peripheral blood mononuclear cell protein expression signal transduction T lymphocyte activation upregulation |
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. https://doi.org/10.3389/fimmu.2018.00416 | 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 | URI: | https://scholarbank.nus.edu.sg/handle/10635/173736 | ISSN: | 16643224 | DOI: | 10.3389/fimmu.2018.00416 |
Appears in Collections: | Staff Publications Elements |
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