ArticleCancer immunology, immunotherapy : CII2013
Inhibitor of apoptosis protein (IAP) antagonists demonstrate divergent immunomodulatory properties in human immune subsets with implications for combination therapy.
Article in Cancer immunology, immunotherapy : CII, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- IAP antagonists induce anti-tumor immunity in multiple myeloma.Nature medicine · 2016Trial
- Cell death in glioblastoma and the central nervous system.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- 3D Tumor Model to Study Immune Cell Infiltration.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Astrocytes and the tumor microenvironment inflammatory state dictate the killing of glioblastoma cells by Smac mimetic compounds.Cell death & disease · 2024Article
- Targeting Upregulated cIAP2 in SOX10-Deficient Drug Tolerant Melanoma.Molecular cancer therapeutics · 2023Article
- Tumor microenvironment mimicking 3D models unveil the multifaceted effects of SMAC mimetics.iScience · 2023Article
- cIAP1/2 Antagonism Induces Antigen-Specific T Cell-Dependent Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- SMAC mimetics inhibit human T cell proliferation and fail to augment type 1 cytokine responses.Cellular immunology · 2023Article
- LCL161 enhances expansion and survival of engineered anti-tumor T cells but is restricted by death signaling.Frontiers in immunology · 2023Article
- A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer.Cancers · 2022Review
- The Immuno-Modulatory Effects of Inhibitor of Apoptosis Protein Antagonists in Cancer Immunotherapy.Cells · 2020Review
- Article
- ASTX660, an antagonist of cIAP1/2 and XIAP, increases antigen processing machinery and can enhance radiation-induced immunogenic cell death in preclinical models of head and neck cancer.Oncoimmunology · 2020Article
- Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice.BMC cancer · 2019Article
- cIAP1/2 inhibition synergizes with TNF inhibition in autoimmunity by down-regulating IL-17A and inducing TScience advances · 2019Article
- Regulation of innate and adaptive antitumor immunity by IAP antagonists.Immunotherapy · 2018Review
- IAP Antagonists Enhance Cytokine Production from Mouse and Human iNKT Cells.Cancer immunology research · 2018Article
- Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs).Apoptosis : an international journal on programmed cell death · 2017Review
- Smac mimetics synergize with immune checkpoint inhibitors to promote tumour immunity against glioblastoma.Nature communications · 2017Article
- The Smac Mimetic BV6 Improves NK Cell-Mediated Killing of Rhabdomyosarcoma Cells by Simultaneously Targeting Tumor and Effector Cells.Frontiers in immunology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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-α-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 naïve 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-κB 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.