Type I interferons and dendritic cells in cancer immunotherapy.

Type I interferons and dendritic cells in cancer immunotherapy. Int Rev Cell Mol Biol. 2019;348:217-262 Authors: Sprooten J, Agostinis P, Garg AD Abstract Type I interferons (IFNs) facilitate cancer immunosurveillance, antitumor immunity and antitumor efficacy of conventional cell death-inducing therapies (chemotherapy/radiotherapy) as well as immunotherapy. Moreover, it is clear that dendritic cells (DCs) play a significant role in aiding type I IFN-driven immunity. Owing to these antitumor properties several immunotherapies involving, or inducing, type I IFNs have received considerable clinical attention, e.g., recombinant IFNα2 or agonists targeting pattern recognition receptor (PRR) pathways like Toll-like receptors (TLRs), cGAS-STING or RIG-I/MDA5/MAVS. A series of preclinical and clinical evidence concurs that the success of anticancer therapy hinges on responsiveness of both cancer cells and DCs to type I IFNs. In this article, we discuss this link between type I IFNs and DCs in the context of cancer biology, with particular attention to mechanisms behind type I IFN production, their impact on DC driven anticancer immunity, and the implications of this for cancer immunotherapy, including DC-based vaccines. PMID: 31810554 [PubMed - in process]
Source: International Review of Cell and Molecular Biology - Category: Cytology Authors: Tags: Int Rev Cell Mol Biol Source Type: research

Related Links:

O'Kane GM, Wilson JM, Knox JJ, Connor A, Wang Y, Zogopoulos G, Gallinger S Abstract PURPOSE: The molecular drivers of antitumor immunity in pancreatic ductal adenocarcinoma (PDAC) are poorly understood, posing a major obstacle for the identification of patients potentially amenable for immune checkpoint blockade or other novel strategies. Here, we explore the association of chemokine expression with effector T cell infiltration in PDAC. EXPERIMENTAL DESIGN: Discovery cohorts comprised 113 primary resected PDAC and 107 PDAC liver metastases. Validation cohorts comprised 182 PDAC from TCGA and 92 PDACs from the...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Authors: Philipp J, Sievert W, Azimzadeh O, von Toerne C, Metzger F, Posch A, Hladik D, Subedi P, Multhoff G, Atkinson MJ, Tapio S Abstract PURPOSE: Pulmonary inflammation is an adverse consequence of radiation therapy in breast cancer. The aim of this study was to elucidate biological pathways leading to this pathology. MATERIALS AND METHODS: Lung endothelial cells were isolated 24 hours after thorax-irradiation (sham or 10 Gy X-ray) from female C57Bl/6 mice and cultivated for 6 days. RESULTS: Quantitative proteomic analysis of lung endothelial cells was done using data independent acquisitio...
Source: International Journal of Radiation Biology - Category: Radiology Tags: Int J Radiat Biol Source Type: research
Abstract Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a predominant DNA sensor inducing the activation of the innate immune responses that produce proinflammatory cytokines and type I interferons, which has been well-investigated in mammals. However, chicken cGAS (chcGAS), which participates in avian innate immunity, has not been well-investigated. Here, we cloned the complete open reading frame sequence of chcGAS. Multiple sequence alignment and phylogenetic analysis revealed that chcGAS was homologous to mammalian cGAS. The chcGAS mRNA was highly expressed in the bone marrow and ileum. The subcellular localization ...
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Tags: Int J Biol Macromol Source Type: research
In conclusion, we found that IFI16 positively regulate PD-L1 through STING-TBK1-NF-kB pathway, thus promoting cervical cancer progression. The roles of IFI16 in cervical cancer progression deserve further investigation and hold the promise of being developed as a novel immunotherapy target in the future.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Abstract STING (Stimulator of Interferon Genes) has become a focal point in immunology research and a target in drug discovery. The discovery of a potent human-STING agonist is expected to revolutionize current anti-virus or cancer immunotherapy. Inspired by the structure and function of murine STING-specific agonists (DMXAA and CMA), we rationally designed and synthesized four series of novel compounds for the enhancement of human sensitivity. In the cell-based assay, we identified six compounds from all the synthetic small molecules: 2g, 9g, and 12b are STING agonists that are efficacious across species, and all...
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research
Contributors : Cameron S Field ; Fran Biaxauli Celda ; Ryan L Kyle ; Alanna M. Cameron ; David E Sanin ; Keli L Hippen ; Michael Loschi ; Daniel J Puleston ; Mauro Corrado ; Joy Edwards-Hicks ; Katarzyna M Grzes ; Edward J Pearce ; Bruce R Blazar ; Erika L PearceSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusRegulatory T cells (Tregs) negatively regulate immune-mediated inflammation that is essential for preventing autoimmunity, but which can be detrimental in cancer. Central to Treg activation are changes in lipid metabolism to support their survival and function. Fatty acid binding...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Conclusion: We confirmed the distinct STING expression in CRC and demonstrated its independent prognostic value in survival outcomes. STING could be a potential therapeutic target that enhances anti-cancer immune response in CRC.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Contributors : Steven Lohard ; Nathalie Bourgeois ; Laurent Maillet ; Fabien Gautier ; Aur élie Fétiveau ; Hamza Lasla ; Frédérique Nguyen ; Céline Vuillier ; Alison Dumont ; Agnès Moreau-Aubry ; Morgane Frapin ; Laurent David ; Delphine Loussouarn ; Olivier Kerdraon ; Mario Campone ; Pascal Jézéquel ; Philippe P Juin ; Sophie Barillé-NionSeries Type : Expression profiling by arrayOrganism : Homo sapiensA fascinating but uncharacterized action of antimitotic chemotherapy is to collectively prime cancer cells to apoptotic mitochondrial outer membrane permeabiliz...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
Abstract The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-pathway triggers innate immune responses by recognizing cytosolic DNA. Recent studies revealed that STING adaptor associates with various diseases, and several modulators targeting STING have been identified including three agonists that have entered clinical trials for treating cancer over the past 2 years. In particular, the efficacy of STING agonists and/or antagonists suggests adaptor STING as a potential therapeutic target for diverse diseases. Herein, we summarize the latest advances in understanding STING functioning and prov...
Source: Drug Discovery Today - Category: Drugs & Pharmacology Authors: Tags: Drug Discov Today Source Type: research
Molecules, Vol. 24, Pages 4192: ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1 Molecules doi: 10.3390/molecules24224192 Authors: Kenneth I. Onyedibe Modi Wang Herman O. Sintim Ectonucleotide pyrophosphatase/phosphodiesterase I (ENPP1) was identified several decades ago as a type II transmembrane glycoprotein with nucleotide pyrophosphatase and phosphodiesterase enzymatic activities, critical for purinergic signaling. Recently, ENPP1 has emerged as a critical phosphodiesterase that degrades the stimulator of interferon genes (STING) ligand, cyclic GMP&am...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
More News: Biology | Cancer | Cancer & Oncology | Cancer Vaccines | Chemotherapy | Cytology | Immunotherapy | Insect Bites & Stings | Molecular Biology | Vaccines