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Background
Anti-cancer effects of HDAC inhibitors were shown to rely on an intact immune system.
Additionally, combination of HDAC inhibitors with different cancer immunotherapy approaches
was shown to be successful, suggesting that HDAC inhibition itself may engage and
mediate an anti-tumoural immune response during cancer therapy.
Aim
Evaluation of immunomodulating effects of the HDAC inhibitor Resminostat, potentially
contributing to its anti-tumoural activity.
Method
Resminostat effects on mechanisms affecting anti-tumoural immune responses were analysed
in hepatocellular HepG2, Huh7, and SNU475 and adenocarcinomic A549 cells.
Results
Resminostat strongly reduced the expression of immunosuppression mediating enzymes,
IDO1 and ARG1. Additionally, Resminostat considerably enhanced the expression of NKG2D
ligands, MHC class I molecules, and several cancer testis antigens on several tumour
cell lines. Interestingly, Resminostat was also able to up-regulate the expression
of MHC class II and co-stimulatory molecule 4-1BBL.
Discussion&conclusions
Resminostat showed promising immunomodulatory effects demonstrating potential synergism
with immunotherapy approaches using opsonizing antibodies (e.g. rituximab), immunostimulating
agents (e.g. cytokines, stimulating antibodies, TLR ligands), and immune checkpoint
blockers (PD1/PDL1 and CTLA-4 inhibitors).
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