scholarly journals Comprehensive analysis of expression profile and prognostic significance of interferon regulatory factors in pancreatic cancer

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Ke Zhang ◽  
Pan-Ling Xu ◽  
Yu-Jie Li ◽  
Shu Dong ◽  
Hui-Feng Gao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Response ◽  
T Cells ◽  
Signaling Pathway ◽  
Expression Profile ◽  
Prognostic Significance ◽  
Receptor Signaling ◽  
Regulatory Factors ◽  
Interferon Regulatory Factors ◽  
Receptor Signaling Pathway

Abstract Background Pancreatic cancer (PC) is a highly lethal disease and an increasing cause of cancer-associated mortality worldwide. Interferon regulatory factors (IRFs) play vital roles in immune response and tumor cellular biological processes. However, the specific functions of IRFs in PC and tumor immune response are far from systematically clarified. This study aimed to explorer the expression profile, prognostic significance, and biological function of IRFs in PC. Results We observed that the levels of IRF2, 6, 7, 8, and 9 were elevated in tumor compared to normal tissues in PC. IRF7 expression was significantly associated with patients’ pathology stage in PC. PC patients with high IRF2, low IRF3, and high IRF6 levels had significantly poorer overall survival. High mRNA expression, amplification and, deep deletion were the three most common types of genetic alterations of IRFs in PC. Low expression of IRF2, 4, 5, and 8 was resistant to most of the drugs or small molecules from Genomics of Drug Sensitivity in Cancer. Moreover, IRFs were positively correlated with the abundance of tumor infiltrating immune cells in PC, including B cells, CD8+ T cells, CD4+ T cells, macrophages, Neutrophil, and Dendritic cells. Functional analysis indicated that IRFs were involved in T cell receptor signaling pathway, immune response, and Toll-like receptor signaling pathway. Conclusions Our results indicated that certain IRFs could serve as potential therapeutic targets and prognostic biomarkers for PC patients. Further basic and clinical studies are needed to validate our findings and generalize the clinical application of IRFs in PC.

scholarly journals Comprehensive Analysis of Expression Profile and Prognostic Significance of Interferon Regulatory Factors in Pancreatic Cancer

2021 ◽  
Author(s):  
Ke Zhang ◽  
Pan-Ling Xu ◽  
Yu-Jie Li ◽  
Shu Dong ◽  
Hui-Feng Gao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Response ◽  
T Cells ◽  
Signaling Pathway ◽  
Expression Profile ◽  
Prognostic Significance ◽  
Receptor Signaling ◽  
Regulatory Factors ◽  
Interferon Regulatory Factors ◽  
Receptor Signaling Pathway

Abstract Background: Pancreatic cancer (PC) is a highly lethal disease and an increasing cause of cancer-associated mortality worldwide. Interferon regulatory factors (IRFs) play vital roles in immune response and tumor cellular biological process. However, the specific functions of IRFs in PC and tumor immune response are far from systematically clarified. This study aimed to explorer the expression profile, prognostic significance, and biological function of IRFs in PC.Results: We observed that the level of IRF3, 6, 7, 8, and 9 were elevated in tumor compared to normal tissues in PC. IRF7 expression was significantly associated with patients’ pathology stage in PC. PC patients with high IRF2, low IRF3, and high IRF6 level had significantly poorer overall survival. High mRNA expression, amplification and deep deletion were the three most common types of genetic alterations of IRFs in PC. Low expression of IRF2, 4, 5, and 8 was resistant to most of the drugs or small molecules from Genomics of Drug Sensitivity in Cancer. Moreover, IRFs were positively correlated with the abundance of tumor infiltrating immune cells in PC, including B cells, CD8+ T cells, CD4+ T cells, macrophages, Neutrophil, and Dendritic cells. Functional analysis indicated that IRFs were involved in T cell receptor signaling pathway, immune response and Toll-like receptor signaling pathway. Conclusions: Our results indicated that certain IRFs could serve as potential therapeutic targets and prognostic biomarker for PC patients. Further basic and clinical studies are needed to validate our findings and generalize the clinical application of IRFs in PC.

scholarly journals Transcriptome Analysis for Genes Associated with Small Ruminant Lentiviruses Infection in Goats of Carpathian Breed

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2054
Author(s):  
Monika Olech ◽  
Katarzyna Ropka-Molik ◽  
Tomasz Szmatoła ◽  
Katarzyna Piórkowska ◽  
Jacek Kuźmak
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Proviral Load ◽  
Cytokine Production ◽  
Small Ruminant ◽  
Receptor Signaling ◽  
Toll Like Receptor ◽  
Receptor Signaling Pathway

Small ruminant lentiviruses (SRLV) are economically important viral pathogens of sheep and goats. SRLV infection may interfere in the innate and adaptive immunity of the host, and genes associated with resistance or susceptibility to infection with SRLV have not been fully recognized. The presence of animals with relatively high and low proviral load suggests that some host factors are involved in the control of virus replication. To better understand the role of the genes involved in the host response to SRLV infection, RNA sequencing (RNA-seq) method was used to compare whole gene expression profiles in goats carrying both a high (HPL) and low (LPL) proviral load of SRLV and uninfected animals. Data enabled the identification of 1130 significant differentially expressed genes (DEGs) between control and LPL groups: 411 between control and HPL groups and 1434 DEGs between HPL and LPL groups. DEGs detected between the control group and groups with a proviral load were found to be significantly enriched in several gene ontology (GO) terms, including an integral component of membrane, extracellular region, response to growth factor, inflammatory and innate immune response, transmembrane signaling receptor activity, myeloid differentiation primary response gene 88 (MyD88)-dependent toll-like receptor signaling pathway as well as regulation of cytokine secretion. Our results also demonstrated significant deregulation of selected pathways in response to viral infection. The presence of SRLV proviral load in blood resulted in the modification of gene expression belonging to the toll-like receptor signaling pathway, the tumor necrosis factor (TNF) signaling pathway, the cytokine-cytokine receptor interaction, the phagosome, the Ras signaling pathway, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) (PI3K-Akt) signaling pathway and rheumatoid arthritis. It is worth mentioning that the most predominant in all pathways were genes represented by toll-like receptors, tubulins, growth factors as well as interferon gamma receptors. DEGs detected between LPL and HPL groups were found to have significantly enriched regulation of signaling receptor activity, the response to toxic substances, nicotinamide adenine dinucleotide (NADH) dehydrogenase complex assembly, cytokine production, vesicle, and vacuole organization. In turn, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway tool classified DEGs that enrich molecular processes such as B and T-cell receptor signaling pathways, natural killer cell-mediated cytotoxicity, Fc gamma R-mediated phagocytosis, toll-like receptor signaling pathways, TNF, mammalian target of rapamycin (mTOR) signaling and forkhead box O (Foxo) signaling pathways, etc. Our data indicate that changes in SRLV proviral load induced altered expression of genes related to different biological processes such as immune response, inflammation, cell locomotion, and cytokine production. These findings provide significant insights into defense mechanisms against SRLV infection. Furthermore, these data can be useful to develop strategies against SRLV infection by selection of animals with reduced SRLV proviral concentration that may lead to a reduction in the spread of the virus.

EXTH-61. MODULATION OF THE IL-27 RECEPTOR SIGNALING PATHWAY IN GLIOBLASTOMA AND ONCOLYTIC VIROTHERAPY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi177-vi177
Author(s):  
Eleni Panagioti ◽  
Michal Nowicki ◽  
William Goins ◽  
Jorge Jimenez Macias ◽  
Julia Escobar ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Signaling Pathway ◽  
Glioma Cells ◽  
Oncolytic Virotherapy ◽  
Receptor Signaling ◽  
Inhibitory Receptors ◽  
Receptor Signaling Pathway ◽  
Hsv 1

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with median overall survival of 14-16 months. Glioblastoma progression involves multiple immunosuppressive pathways hindering the success of cancer immunotherapy. Oncolytic virotherapy is a promising approach to reprogram the glioblastoma microenvironment and restore anti-tumor immunity. Interleukin (IL)-27 receptor signaling pathway regulates development of effector T cells, IL-10 producing T regulatory type 1 (Tr1) cells and induction of co-inhibitory receptors associated with T cell exhaustion in cancer. In this study, we sought to tackle local and systemic GBM-induced immunosuppression using the novel rQNestin34.5v2 oncolytic herpes simplex virus type-1 (HSV-1), engineered to selectively replicate in glioma cells together with genetic disruptions of the IL-27 receptor signaling pathway. The antitumor activity of HSV-1 rQNestin34.5v2 was evaluated in IL-27ra-/- and wild-type C57BL/6 mice harboring orthotopic CT-2A and GL261 glioblastoma and in athymic nude mice harboring orthotopic patient derived glioblastoma xenografts (PDXs) selected from patients that had been treated in a clinical trial of intratumoral administration of HSV-1 rQNestin34.5v2 (ClinicalTrials.gov: NCT03152318). HSV-1 rQNestin34.5v2 exhibited superior capacity to infect glioma cells in vitro triggering release of proinflammatory cytokines and inducing immunogenic cell death in infected cells. Immune phenotyping of GL261 and CT-2A gliomas revealed astrocytes and microglia express the highest levels of IL-27R. Lack of IL-27R signaling decreased expression of the co-inhibitory receptors PD-1 and Tim-3 on circulating CD4+ T cells suggesting altered CD4+ T cell responses. In the tumor microenvironment, lack of IL-27R signaling decreased immune suppression as evidenced by reduced interleukin (IL)-10 secretion by glioma cells. Despite positive functional modifications on CD4+ T cells, global lack of IL-27R signaling promoted tumor growth accompanied by increased circulating myeloid derived suppressor cells (MDSCs) in the GL261 model. Experiments to address the immunoregulatory role of IL-27R signaling during HSV-1 rQNestin34.5v2 virotherapy-induced glioma tissue destruction are ongoing.

scholarly journals The Molecular Mechanism of Hemocyte Immune Response in Marsupenaeus japonicus Infected With Decapod Iridescent Virus 1

2021 ◽  
Vol 12 ◽  
Author(s):  
Zihao He ◽  
Jichen Zhao ◽  
Xieyan Chen ◽  
Minze Liao ◽  
Yuan Xue ◽  
...  
Keyword(s):  
Immune Response ◽  
Enzyme Activity ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Replication Initiation ◽  
Economic Losses ◽  
Receptor Signaling ◽  
Marsupenaeus Japonicus ◽  
Iridescent Virus ◽  
Receptor Signaling Pathway

As a new type of shrimp lethal virus, decapod iridescent virus 1 (DIV1) has caused huge economic losses to shrimp farmers in China. Up to now, DIV1 has been detected in a variety of shrimps, but there is no report in Marsupenaeus japonicus. In the current study, we calculated the LC50 to evaluate the toxicity of DIV1 to M. japonicus and determined through nested PCR that M. japonicus can be the host of DIV1. Through enzyme activity study, it was found that DIV1 can inhibit the activities of superoxide dismutase, catalase, lysozyme, and phenoloxidase, which could be a way for DIV1 to achieve immune evasion. In a comprehensive study on the transcriptomic changes of M. japonicus in response to DIV1 infection, a total of 52,287 unigenes were de novo assembled, and 20,342 SSR markers associated with these unigenes were obtained. Through a comparative transcriptomic analysis, 6,900 differentially expressed genes were identified, including 3,882 upregulated genes and 3,018 downregulated genes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that some GO terms related to virus invasion, replication, and host antiviral infection were promoted under DIV1 infection, such as carbohydrate binding, chitin binding, chitin metabolic process, and DNA replication initiation, and some KEGG pathways related to immune response were significantly influenced by DIV1 infection, including Toll and IMD signaling pathway, JAK-STAT signaling pathway, IL-17 signaling pathway, C-type lectin receptor signaling pathway, complement and coagulation cascades, antigen processing and presentation, necroptosis, apoptosis, NOD-like receptor signaling pathway, apoptosis—multiple species, and TNF signaling pathway. Further analysis showed that STAT, Dorsal, Relish, heat shock protein 70 (HSP70), C-type lectins, and caspase play an important role in DIV1 infection. This is the first detailed study of DIV1 infection in M. japonicus, which initially reveals the molecular mechanism of DIV1 infection in M. japonicus by using the transcriptome analysis of hemocytes combined with enzyme activity study.

scholarly journals T cell receptor signaling pathway is overexpressed in CD4+ T cells from HAM/TSP individuals

2015 ◽  
Vol 19 (6) ◽  
pp. 578-584 ◽  
Author(s):  
Mariana Tomazini Pinto ◽  
Tathiane Maistro Malta ◽  
Evandra Strazza Rodrigues ◽  
Osvaldo Massaiti Takayanagui ◽  
Yuetsu Tanaka ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Signaling Pathway ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Receptor Signaling ◽  
T Cell Receptor Signaling ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling
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