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| rdf:type
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| rdfs:seeAlso
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| Description
| - Inhibitor of apoptosis proteins (IAPs) are critical in regulating apoptosis resistance in cancer. Antagonists of IAPs, such as LCL161, are in clinical development and show promise as anti-cancer agents for solid and hematological cancers, with preliminary data suggesting they may act as immunomodulators. IAP antagonists hypersensitize tumor cells to TNF-alpha-mediated apoptosis, an effect that may work in synergy with that of cancer vaccines. This study aimed to further investigate the immunomodulatory properties of LCL161 on human immune subsets. T lymphocytes treated with LCL161 demonstrated significantly enhanced cytokine secretion upon activation, with little effect on CD4 and CD8 T-cell survival or proliferation. LCL161 treatment of peripheral blood mononuclear cells significantly enhanced priming of na < ve T cells with synthetic peptides in vitro. Myeloid dendritic cells underwent phenotypic maturation upon IAP antagonism and demonstrated a reduced capacity to cross-present a tumor antigen-based vaccine. These effects are potentially mediated through an observed activation of the canonical and non-canonical NF-kappa B pathways, following IAP antagonism with a resulting upregulation of anti-apoptotic molecules. In conclusion, this study demonstrated the immunomodulatory properties of antagonists at physiologically relevant concentrations and indicates their combination with immunotherapy requires further investigation.
- Inhibitor of apoptosis proteins (IAPs) are critical in regulating apoptosis resistance in cancer. Antagonists of IAPs, such as LCL161, are in clinical development and show promise as anti-cancer agents for solid and hematological cancers, with preliminary data suggesting they may act as immunomodulators. IAP antagonists hypersensitize tumor cells to TNF-alpha-mediated apoptosis, an effect that may work in synergy with that of cancer vaccines. This study aimed to further investigate the immunomodulatory properties of LCL161 on human immune subsets. T lymphocytes treated with LCL161 demonstrated significantly enhanced cytokine secretion upon activation, with little effect on CD4 and CD8 T-cell survival or proliferation. LCL161 treatment of peripheral blood mononuclear cells significantly enhanced priming of na < ve T cells with synthetic peptides in vitro. Myeloid dendritic cells underwent phenotypic maturation upon IAP antagonism and demonstrated a reduced capacity to cross-present a tumor antigen-based vaccine. These effects are potentially mediated through an observed activation of the canonical and non-canonical NF-kappa B pathways, following IAP antagonism with a resulting upregulation of anti-apoptotic molecules. In conclusion, this study demonstrated the immunomodulatory properties of antagonists at physiologically relevant concentrations and indicates their combination with immunotherapy requires further investigation. (en)
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| Title
| - Inhibitor of apoptosis protein (IAP) antagonists demonstrate divergent immunomodulatory properties in human immune subsets with implications for combination therapy
- Inhibitor of apoptosis protein (IAP) antagonists demonstrate divergent immunomodulatory properties in human immune subsets with implications for combination therapy (en)
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| skos:prefLabel
| - Inhibitor of apoptosis protein (IAP) antagonists demonstrate divergent immunomodulatory properties in human immune subsets with implications for combination therapy
- Inhibitor of apoptosis protein (IAP) antagonists demonstrate divergent immunomodulatory properties in human immune subsets with implications for combination therapy (en)
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| skos:notation
| - RIV/00216208:11130/13:10209795!RIV14-MZ0-11130___
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| http://linked.open...avai/predkladatel
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/00216208:11130/13:10209795
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - Cross-presentation; Dendritic cell; Immunomodulatory; SMAC mimetic; IAP antagonist (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
| - Cancer Immunology, Immunotherapy
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| http://linked.open...in/vavai/riv/obor
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| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
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| http://linked.open...vavai/riv/projekt
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| http://linked.open...UplatneniVysledku
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| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Fučíková, Jitka
- Cebon, Jonathan
- Knights, Ashley J.
- Koernig, Sandra
- Pasam, Anupama
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| http://linked.open...ain/vavai/riv/wos
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| issn
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| number of pages
| |
| http://bibframe.org/vocab/doi
| - 10.1007/s00262-012-1342-1
|
| http://localhost/t...ganizacniJednotka
| |
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