scholarly journals Uncovering the underlying mechanism of cancer tumorigenesis and development under an immune microenvironment from global quantification of the landscape

2017 ◽  
Vol 14 (131) ◽  
pp. 20170105 ◽  
Author(s):  
Li Wenbo ◽  
Jin Wang
Keyword(s):  
Immune System ◽  
Global Sensitivity Analysis ◽  
Underlying Mechanism ◽  
Specific Cell ◽  
Combination Immunotherapy ◽  
Immune Microenvironment ◽  
Recovery Processes ◽  
Cancer Immunity ◽  
Underlying Mechanisms ◽  
Equilibrium Phases

The study of the cancer–immune system is important for understanding tumorigenesis and the development of cancer and immunotherapy. In this work, we build a comprehensive cancer–immune model including both cells and cytokines to uncover the underlying mechanism of cancer immunity based on landscape topography. We quantify three steady-state attractors, normal state, low cancer state and high cancer state, for the innate immunity and adaptive immunity of cancer. We also illustrate the cardinal inhibiting cancer immunity interactions and promoting cancer immunity interactions through global sensitivity analysis. We simulate tumorigenesis and the development of cancer and classify these into six stages. The characteristics of the six stages can be classified further into three groups. These correspond to the escape, elimination and equilibrium phases in immunoediting, respectively. Under specific cell–cell interactions strength oscillations emerge. We found that tumorigenesis and cancer recovery processes may need to go through cancer–immune oscillation, which consumes more energy. Based on the cancer–immune landscape, we predict three types of cells and two types of cytokines for cancer immunotherapy as well as combination immunotherapy. This landscape framework provides a quantitative way to understand the underlying mechanisms of the interplay between cancer and the immune system for cancer tumorigenesis and development.

scholarly journals Innovation in NLR and TLR sensing drives the MHC-II free Atlantic cod immune system

2020 ◽  
Author(s):  
Xingkun Jin ◽  
Bernat Morro ◽  
Ole K. Tørresen ◽  
Visila Moiche ◽  
Monica H. Solbakken ◽  
...  
Keyword(s):  
Immune System ◽  
Mhc Class Ii ◽  
Atlantic Cod ◽  
Ex Vivo ◽  
Specific Cell ◽  
Major Response ◽  
History Of ◽  
Underlying Mechanisms ◽  
Molecular Patterns ◽  
Cluster Of Differentiation

AbstractThe genome sequencing of Atlantic cod revealed an immune system absent of specific cell surface toll-like receptors (TLRs), major histocompatibility complex (MHC) class II, invariant chain (CD74) and the CD4 (cluster of differentiation 4) receptor. Despite the loss of these major components considered as critical to vertebrate innate and adaptive immune systems the cod system is fully functional, however the underlying mechanisms of the immune response in cod remain largely unknown. In this study, ex vivo cod macrophages were challenged with various bacterial and viral microbe-associated molecular patterns (MAMP) to identify major response pathways. Cytosolic MAMP-PRR pathways based upon the NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) were identified as the critical response pathways. Our analyses suggest that internalization of exogenous ligands through scavenger receptors drives both pathways activating transcription factors like NF-kB (Nuclear factor-kappa B) and interferon regulatory factors (IRFs). Further, ligand-dependent differential expression of a unique TLR25 isoform and multiple NLR paralogues suggests (sub)neofunctionalisation toward specific immune defensive strategies. Our results further demonstrate that the unique immune system of the Atlantic cod provides an unprecedented opportunity to explore the evolutionary history of PRR-based signalling in vertebrate immunity.

Contrasting underlying mechanisms of different barrier coating types

TAPPI Journal ◽  
2018 ◽  
Vol 17 (01) ◽  
pp. 31-37
Author(s):  
Bryan McCulloch ◽  
John Roper ◽  
Kaitlin Rosen
Keyword(s):  
Food Packaging ◽  
Underlying Mechanism ◽  
Consumer Products ◽  
Mechanical Degradation ◽  
Design Rules ◽  
Barrier Coatings ◽  
Barrier Materials ◽  
Barrier Coating ◽  
Coating Type ◽  
Underlying Mechanisms

Barrier coatings are used in applications including food packaging, dry goods, and consumer products to prevent transport of different compounds either through or into paper and paperboard substrates. These coatings are useful in packaging to contain active ingredients, such as fragrances, or to protect contents from detrimental substances, such as oxygen, water, grease, or other chemicals of concern. They also are used to prevent visual changes or mechanical degradation that might occur if the paper becomes saturated. The performance and underlying mechanism depends on the barrier coating type and, in particular, on whether the barrier coating is designed to prevent diffusive or capillary transport. Estimates on the basis of fundamental transport phenomena and data from a broad screening of different barrier materials can be used to understand the limits of various approaches to construct barrier coatings. These estimates also can be used to create basic design rules for general classes of barrier coatings.

scholarly journals MITF induces escape from innate immunity in melanoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Luis Sánchez-del-Campo ◽  
Román Martí-Díaz ◽  
María F. Montenegro ◽  
Rebeca González-Guerrero ◽  
Trinidad Hernández-Caselles ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nk Cells ◽  
Nk Cell ◽  
Luciferase Reporter ◽  
Damage Repair ◽  
Reporter Assays ◽  
Underlying Mechanisms ◽  
Nk Cytotoxicity

Abstract Background The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. Methods By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. Results Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. Conclusion Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies.

scholarly journals Pan-cancer characterization of lncRNA modifiers of immune microenvironment reveals clinically distinct de novo tumor subtypes

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zicheng Zhang ◽  
Congcong Yan ◽  
Ke Li ◽  
Siqi Bao ◽  
Lei Li ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Immune Cell ◽  
De Novo ◽  
Solid Cancer ◽  
Immune Microenvironment ◽  
Cancer Subtypes ◽  
Tumor Subtypes ◽  
Cancer Immunity ◽  
Systems Immunology ◽  
Pan Cancer

AbstractThe emerging field of long noncoding RNA (lncRNA)-immunity has provided a new perspective on cancer immunity and immunotherapies. The lncRNA modifiers of infiltrating immune cells in the tumor immune microenvironment (TIME) and their impact on tumor behavior and disease prognosis remain largely uncharacterized. In the present study, a systems immunology framework integrating the noncoding transcriptome and immunogenomics profiles of 9549 tumor samples across 30 solid cancer types was used, and 36 lncRNAs were identified as modifier candidates underlying immune cell infiltration in the TIME at the pan-cancer level. These TIME lncRNA modifiers (TIL-lncRNAs) were able to subclassify various tumors into three de novo pan-cancer subtypes characterized by distinct immunological features, biological behaviors, and disease prognoses. Finally, a TIL-lncRNA-derived immune state index (TISI) that was reflective of immunological and oncogenic states but also predictive of patients’ prognosis was proposed. Furthermore, the TISI provided additional prognostic value for existing tumor immunological and molecular subtypes. By applying the TISI to tumors from different clinical immunotherapy cohorts, the TISI was found to be significantly negatively correlated with immune-checkpoint genes and to have the ability to predict the effectiveness of immunotherapy. In conclusion, the present study provided comprehensive resources and insights for future functional and mechanistic studies on lncRNA-mediated cancer immunity and highlighted the potential of the clinical application of lncRNA-based immunotherapeutic strategies in precision immunotherapy.

scholarly journals An Evidence for a Novel Antiviral Mechanism of Teleost Fish: Serum-Derived Exosomes Inhibit Virus Replication Through Incorporating Mx1 Protein

2021 ◽  
Author(s):  
Changjun Guo ◽  
Jian He ◽  
Zhi-Min Li ◽  
Yuanyuan Wang ◽  
Chen nan nan ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Teleost Fish ◽  
Protein Composition ◽  
Underlying Mechanism ◽  
Antiviral Effect ◽  
Mandarin Fish ◽  
Underlying Mechanisms ◽  
Antiviral Mechanism ◽  
Fish Serum

Exosomes are associated with cancer progression, pregnancy, cardiovascular diseases, central nervous system–related diseases, immune responses and viral pathogenicity. However, study on the role of exosomes in the immune response of teleost fish, especially antiviral immunity, is limited. Herein, serum-derived exosomes from mandarin fish were used to investigate antiviral effect for the exosomes of teleost fish. Exosomes were isolated from mandarin fish serum by ultracentrifugation could internalize into Mandarin fish fry (MFF-1) cells and inhibited Infectious spleen and kidney necrosis virus (ISKNV) infection. To further investigated the underlying mechanisms of exosomes in inhibiting ISKNV infection. The protein composition of serum-derived exosomes was by analysis mass spectrometry and found that myxovirus resistance 1 (Mx1) was incorporated in the exosomes. Furthermore, the scMx1 protein was proved transferred to the recipient cells though the exosomes. Our results found that the serum-derived exosomes from mandarin fish could inhibit ISKNV replication and suggested an underlying mechanism of the serum-derived exosomes antivirus is that serum-derived exosomes incorporation of the Mx1 protein into exosomes and delivery into recipient cells. This study provided an evidence for the important antiviral role of exosomes in the immune system of teleost fish.

D-alanine metabolism via D-Ala aminotransferase by marine Gammaproteobacteria , Pseudoalteromonas sp. CF6-2

2021 ◽  
Author(s):  
Yang Yu ◽  
Jie Yang ◽  
Zhao-Jie Teng ◽  
Li-Yuan Zheng ◽  
Qi Sheng ◽  
...  
Keyword(s):  
Amino Acid ◽  
Marine Bacteria ◽  
Gene Knockout ◽  
Underlying Mechanism ◽  
Dominant Group ◽  
Seawater Samples ◽  
Underlying Mechanisms ◽  
Biochemical Analyses ◽  
Global Oceans ◽  
Shed Light

As the most abundant D-amino acid (DAA) in the ocean, D-alanine (D-Ala) is a key component of peptidoglycan in bacterial cell wall. However, the underlying mechanisms of bacterial metabolization of D-Ala through microbial food web remain largely unknown. In this study, the metabolism of D-Ala by marine bacterium Pseudoalteromonas sp. CF6-2 was investigated. Based on genomic, transcriptional and biochemical analyses combined with gene knockout, D-Ala aminotransferase was found to be indispensable for the catabolism of D-Ala in strain CF6-2. Investigation on other marine bacteria also showed that D-Ala aminotransferase gene is a reliable indicator for their ability to utilize D-Ala. Bioinformatic investigation revealed that D-Ala aminotransferase sequences are prevalent in genomes of marine bacteria and metagenomes, especially in seawater samples, and Gammaproteobacteria represents the predominant group containing D-Ala aminotransferase. Thus, Gammaproteobacteria is likely the dominant group to utilize D-Ala via D-Ala aminotransferase to drive the recycling and mineralization of D-Ala in the ocean. IMPORTANCE As the most abundant D-amino acid in the ocean, D-Ala is a component of marine DON (Dissolved organic nitrogen) pool. However, the underlying mechanism of bacterial metabolization of D-Ala to drive the recycling and mineralization of D-Ala in the ocean is still largely unknown. The results in this study showed that D-Ala aminotransferase is specific and indispensable for D-Ala catabolism in marine bacteria, and that marine bacteria containing D-Ala aminotransferase genes are predominantly Gammaproteobacteria widely distributed in global oceans. This study reveals marine D-Ala utilizing bacteria and the mechanism of their metabolization of D-Ala. The results shed light on the mechanisms of recycling and mineralization of D-Ala driven by bacteria in the ocean, which are helpful in understanding oceanic microbial-mediated nitrogen cycle.

scholarly journals Toxicity Reduction of Euphorbia kansui Stir-Fried with Vinegar Based on Conversion of 3-O-(2′E,4′Z-Decadi-enoyl)-20-O-acetylingenol

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3806 ◽  
Author(s):  
Qiao Zhang ◽  
Yi Zhang ◽  
Shi-Kang Zhou ◽  
Kan Wang ◽  
Min Zhang ◽  
...  
Keyword(s):  
High Performance ◽  
Developmental Toxicity ◽  
Underlying Mechanism ◽  
Severe Toxicity ◽  
Sod Activity ◽  
Mechanisms Of Toxicity ◽  
Toxicity Reduction ◽  
Euphorbia Kansui ◽  
The Difference ◽  
Underlying Mechanisms

The dried roots of Euphorbia kansui S.L.Liou ex S.B.Ho have long been used to treat edema in China. However, the severe toxicity caused by Euphorbia kansui (EK) has seriously restricted its clinical application. Although EK was processed with vinegar to reduce its toxicity, the detailed mechanisms of attenuation in toxicity of EK stir-fried with vinegar (VEK) have not been well delineated. Diterpenoids are the main toxic ingredients of EK, and changes in these after processing may be the underlying mechanism of toxicity attenuation of VEK. 3-O-(2′E,4′Z-decadienoyl)-20-O-acetylingenol (3-O-EZ) is one of the diterpenoids derived from EK, and the content of 3-O-EZ was significantly reduced after processing. This study aims to explore the underlying mechanisms of toxicity reduction of VEK based on the change of 3-O-EZ after processing with vinegar. Based on the chemical structure of 3-O-EZ and the method of processing with vinegar, simulation experiments were carried out to confirm the presence of the product both in EK and VEK and to enrich the product. Then, the difference of peak area of 3-O-EZ and its hydrolysate in EK and VEK were detected by ultra-high-performance liquid chromatography (UPLC). Furthermore, the toxicity effect of 3-O-EZ and its hydrolysate, as well as the underlying mechanism, on zebrafish embryos were investigated. The findings showed that the diterpenoids (3-O-EZ) in EK can convert into less toxic ingenol in VEK after processing with vinegar; meanwhile, the content of ingenol in VEK was higher than that of EK. More interestingly, the ingenol exhibited less toxicity (acute toxicity, developmental toxicity and organic toxicity) than that of 3-O-EZ, and 3-O-EZ could increase malondialdehyde (MDA) content and reduce glutathione (GSH) content; cause embryo oxidative damage by inhibition of the succinate dehydrogenase (SDH) and superoxide dismutase (SOD) activity; and induce inflammation and apoptosis by elevation of IL-2 and IL-8 contents and activation of the caspase-3 and caspase-9 activity. Thus, this study contributes to our understanding of the mechanism of attenuation in toxicity of VEK, and provides the possibility of safe and rational use of EK in clinics.

scholarly journals A Fragrant Environment Containing α-Pinene Suppresses Tumor Growth in Mice by Modulating the Hypothalamus/Sympathetic Nerve/Leptin Axis and Immune System

2019 ◽  
Vol 18 ◽  
pp. 153473541984513 ◽  
Author(s):  
Masatoshi Kusuhara ◽  
Koji Maruyama ◽  
Hidee Ishii ◽  
Yoko Masuda ◽  
Kazutoshi Sakurai ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Tumor Growth ◽  
Sympathetic Nerve ◽  
Stress Hormones ◽  
Nervous Activity ◽  
Underlying Mechanism ◽  
Plasma Corticosterone ◽  
Sympathetic Nervous Activity ◽  
Immunological Parameters

The environment is thought to affect outcomes in patients with cancer; however, this relationship has not been proven directly. Recently, an enriched environment, as a model of a positive environment, has been shown to suppress tumor growth by lowering leptin production through a pathway involving the hypothalamus/sympathetic nerve/leptin axis. We previously reported that a fragrant environment (FE) containing α-pinene suppressed tumor growth in mice; however, the underlying mechanism has not been elucidated. Accordingly, in this study, we investigated changes in the neuroendocrine and immune systems following exposure to an FE. Mice were exposed to α-pinene (5 h/day) for 4 weeks prior to tumor implantation with murine melanoma cells and 3 weeks after transplantation. In addition to the evaluation of tumor growth, the blood, spleen, and hypothalamus were collected 3 weeks after transplantation, and neuroendocrinological and immunological parameters were measured. Tumor size was ~40% smaller in mice exposed to FE. Moreover, plasma noradrenaline concentrations, which reflected sympathetic nervous activity, tended to increase, and leptin levels were significantly decreased in FE-exposed mice. Levels of stress hormones, such as plasma corticosterone and adrenaline, did not change in the 2 groups. In the hypothalamus, brain-derived neurotrophic factor protein levels and glucose-1-phosphate concentrations were decreased in the FE group. Additionally, numbers of B cells, CD4+ T cells, CD8+ T cells, and natural killer cells increased in the FE-exposed mice. These neurohormonal and immunological changes in the FE-exposed mice suggested that the FE may activate the hypothalamus/sympathetic nerve/leptin axis and immune system, thereby retarding tumor growth.

scholarly journals Combination immunotherapy and active-specific tumor cell vaccination augments anti-cancer immunity in a mouse model of gastric cancer

2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Natasja K van den Engel ◽  
Dominik Rüttinger ◽  
Margareta Rusan ◽  
Robert Kammerer ◽  
Wolfgang Zimmermann ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mouse Model ◽  
Tumor Cell ◽  
Combination Immunotherapy ◽  
Cancer Immunity ◽  
Specific Tumor ◽  
Anti Cancer

scholarly journals Acute sickness behaviour: an immune system-to-brain communication?

2001 ◽  
Vol 31 (5) ◽  
pp. 761-767 ◽  
Author(s):  
UTÉ VOLLMER-CONNA
Keyword(s):  
Immune System ◽  
Current Knowledge ◽  
Large Body ◽  
Adaptive Function ◽  
Sickness Behaviour ◽  
Specific Symptom ◽  
Seminal Paper ◽  
The Subject ◽  
Underlying Mechanisms ◽  
The Brain

Over the past 20 years, psychoneuroimmunological research has produced a large body of evidence that challenges the historically dominant view that the immune system operates in an autonomous manner independent of other physiological systems. Today, there is little doubt that the brain and the immune system are intimately linked and capable of reciprocal communication (Ader et al. 1991). Despite the acknowledged bi-directional nature of the brain–immune system connection, the predominant focus of study has been on the effects of psychological and behavioural events (e.g. stress) on immune responses and disease processes, and the mechanisms underlying such effects (see Kusnekov & Rabin, 1994; Maier et al. 1994; Rozlog et al. 1999). However, considerable interest in the possibilities of immune-system-to-brain communication was initiated by a seminal paper considering the biological basis of behaviour in sick animals (Hart, 1988). Subsequently, the immunological determinants of the behavioural, cognitive and emotional changes associated with acute illness, as well as with more chronic psychopathological states (e.g. depression) have become the subject of rapidly expanding areas of research (e.g. Kent et al. 1992; Lloyd et al. 1992; Hickie & Lloyd, 1995; Maes et al. 1995a; Rothwell & Hopkins, 1995; Dantzer et al. 1996; Maier & Watkins, 1998; Vollmer-Conna et al. 1998; Maes, 1999).The main objective of this editorial is to provide a succinct overview of current knowledge of the normal behavioural correlates of acute infective illness, their adaptive function and underlying mechanisms. Elucidation of the processes involved in the appearance, maintenance and inhibition of ‘normal’ sickness behaviour is important if extrapolations from this phenomenon to more chronic psychopathological conditions are to provide more than a new label for poorly understood non-specific symptom clusters.

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