Characterizing the role of monocytes in T cell cancer immunotherapy using a 3d microfluidic model
Abstract
In the hepatitis-B virus-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 (TCR)-redirected T cells are similarly inhibited. We thus 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 pre-clinical setting, that can thus be used to improve current immunotherapy strategies.
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BibTeX
@article{wong2026characterizing,
title = {{Characterizing the role of monocytes in T cell cancer immunotherapy using a 3d microfluidic model}},
author = {Siew Cheng Wong and Sharon Wei Ling Lee and Giulia Adriani and Erica Ceccarello and Andrea Pavesi and Anthony Tanoto Tan and Antonio Bertoletti and Roger Dale Kamm},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2018.00416},
url = {https://hal.science/hal-05776445v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Characterizing the role of monocytes in T cell cancer immunotherapy using a 3d microfluidic model
AU - Siew Cheng Wong
AU - Sharon Wei Ling Lee
AU - Giulia Adriani
AU - Erica Ceccarello
AU - Andrea Pavesi
AU - Anthony Tanoto Tan
AU - Antonio Bertoletti
AU - Roger Dale Kamm
PY - 2026
DA - 2026/10/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2018.00416
UR - https://hal.science/hal-05776445v1
AB - In the hepatitis-B virus-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 (TCR)-redirected T cells are similarly inhibited. We thus 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 pre-clinical setting, that can thus be used to improve current immunotherapy strategies.
SN - 1664-3224
SN - 1664-3224
ER -