scholarly journals Role of dendritic cell metabolic reprogramming in tumor immune evasion

2020 ◽  
Vol 32 (7) ◽  
pp. 485-491 ◽  
Author(s):  
Michael P Plebanek ◽  
Michael Sturdivant ◽  
Nicholas C DeVito ◽  
Brent A Hanks
Keyword(s):  
Dendritic Cell ◽  
Metabolic Pathways ◽  
Checkpoint Inhibitor ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Combination Immunotherapy ◽  
Tumor Immune Evasion ◽  
Effector T Cell ◽  
Cell Responses

Abstract The dendritic cell (DC) is recognized as a vital mediator of anti-tumor immunity. More recent studies have also demonstrated the important role of DCs in the generation of effective responses to checkpoint inhibitor immunotherapy. Metabolic programming of DCs dictates their functionality and can determine which DCs become immunostimulatory versus those that develop a tolerized phenotype capable of actively suppressing effector T-cell responses to cancers. As a result, there is great interest in understanding what mechanisms have evolved in cancers to alter these metabolic pathways, thereby allowing for their continued progression and metastasis. The therapeutic strategies developed to reverse these processes of DC tolerization in the tumor microenvironment represent promising candidates for future testing in combination immunotherapy clinical trials.

scholarly journals Role of Immunotherapy in Pulmonary Angiosarcoma: A Case Report

2021 ◽  
pp. 797-801
Author(s):  
Quang Tien Nguyen ◽  
Anh Tuan Pham ◽  
Thuy Thi Nguyen ◽  
Tam Thi Thanh Nguyen ◽  
Ky Van Le
Keyword(s):  
Case Report ◽  
Poor Prognosis ◽  
Checkpoint Inhibitor ◽  
Therapeutic Strategies ◽  
Clinical Entity ◽  
Rare Clinical Entity ◽  
Excellent Response ◽  
First Case

Pulmonary angiosarcoma is a rare clinical entity with a poor prognosis and no established therapeutic strategies. We present the first case to our knowledge of metastatic pulmonary angiosarcoma, treated with checkpoint inhibitor immunotherapy, and have an excellent response. Until now, patient has been treated with immunotherapy for 1 year, and his disease is stable and well-tolerated.

Smith–Magenis syndrome: haploinsufficiency of RAI1 results in altered gene regulation in neurological and metabolic pathways

2011 ◽  
Vol 13 ◽  
Author(s):  
Sarah H. Elsea ◽  
Stephen R. Williams
Keyword(s):  
Metabolic Pathways ◽  
Gene Dosage ◽  
Therapeutic Strategies ◽  
Molecular Evidence ◽  
Diagnostic Strategies ◽  
Functional Studies ◽  
Molecular Features ◽  
Altered Gene ◽  
Behavioural Management

Smith–Magenis syndrome (SMS) is a complex neurobehavioural disorder characterised by intellectual disability, self-injurious behaviours, sleep disturbance, obesity, and craniofacial and skeletal anomalies. Diagnostic strategies are focused towards identification of a 17p11.2 microdeletion encompassing the gene RAI1 (retinoic acid induced 1) or a mutation of RAI1. Molecular evidence shows that most SMS features are due to RAI1 haploinsufficiency, whereas variability and severity are modified by other genes in the 17p11.2 region for 17p11.2 deletion cases. The functional role of RAI1 is not completely understood, but it is probably a transcription factor acting in several different biological pathways that are dysregulated in SMS. Functional studies based on the hypothesis that RAI1 acts through phenotype-specific pathways involving several downstream genes have shown that RAI1 gene dosage is crucial for normal regulation of circadian rhythm, lipid metabolism and neurotransmitter function. Here, we review the clinical and molecular features of SMS and explore more recent studies supporting possible therapeutic strategies for behavioural management.

SARS-Coronavirus 2, A Metabolic Reprogrammer: A Review in the Context of the Possible Therapeutic Strategies

2021 ◽  
Vol 22 ◽  
Author(s):  
Poornima Gopi ◽  
TR Anju ◽  
Vinod Soman Pillai ◽  
Mohanan Veettil
Keyword(s):  
Virus Infection ◽  
Host Cell ◽  
Metabolic Pathways ◽  
Inflammatory Responses ◽  
Membrane Lipid ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Multiple Organs ◽  
The Cross ◽  
The Impact

: Novel coronavirus, SARS-CoV-2 is advancing at a staggering pace to devastate the health care system and foster the concerns over public health. In contrast to the past outbreaks, coronaviruses aren’t clinging themselves as a strict respiratory virus. Rather, becoming a multifaceted virus, it affects multiple organs by interrupting a number of metabolic pathways leading to significant rates of morbidity and mortality. Following infection they rigorously reprogram multiple metabolic pathways of glucose, lipid, protein, nucleic acid and their metabolites to extract adequate energy and carbon skeletons required for their existence and further molecular constructions inside a host cell. Although the mechanism of these alterations are yet to be known, the impact of these reprogramming is reflected in the hyper inflammatory responses, so called cytokine storm and the hindrance of host immune defence system. The metabolic reprogramming during SARS-CoV-2 infection needs to be considered while devising therapeutic strategies to combat the disease and its further complication. The inhibitors of cholesterol and phospholipids synthesis and cell membrane lipid raft of the host cell can, to a great extent, control the viral load and further infection. Depletion of energy source by inhibiting the activation of glycolytic and hexoseamine biosynthetic pathway can also augment the antiviral therapy. The cross talk between these pathways also necessitates the inhibition of amino acid catabolism and tryptophan metabolism. A combinatorial strategy which can address the cross talks between the metabolic pathways might be more effective than a single approach and the infection stage and timing of therapy will also influence the effectiveness of the antiviral approach. We herein focus on the different metabolic alterations during the course of virus infection that help to exploit the cellular machinery and devise a therapeutic strategy which promotes resistance to viral infection and can augment body’s antivirulence mechanisms. This review may cast the light into the possibilities of targeting altered metabolic pathways to defend virus infection in a new perspective.

scholarly journals Energy metabolism manipulates the fate and function of tumour myeloid-derived suppressor cells

2019 ◽  
Vol 122 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Cong Hu ◽  
Bo Pang ◽  
Guangzhu Lin ◽  
Yu Zhen ◽  
Huanfa Yi
Keyword(s):  
Metabolic Pathways ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Metabolic Energy ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Responses ◽  
And Function ◽  
Promote Tumour Development

AbstractIn recent years, a large number of studies have been carried out in the field of immune metabolism, highlighting the role of metabolic energy reprogramming in altering the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathological conditions, such as cancer, inflammation, and infection, and show remarkable ability to suppress T-cell responses. These cells can also change their metabolic pathways in response to various pathogen-derived or inflammatory signals. In this review, we focus on the roles of glucose, fatty acid (FA), and amino acid (AA) metabolism in the differentiation and function of MDSCs in the tumour microenvironment, highlighting their potential as targets to inhibit tumour growth and enhance tumour immune surveillance by the host. We further highlight the remaining gaps in knowledge concerning the mechanisms determining the plasticity of MDSCs in different environments and their specific responses in the tumour environment. Therefore, this review should motivate further research in the field of metabolomics to identify the metabolic pathways driving the enhancement of MDSCs in order to effectively target their ability to promote tumour development and progression.

PS3-08 Role of IL-1 and TNF in human monocyte-derived dendritic cell responses following beta-glucan and LPS stimulation

Cytokine ◽  
2010 ◽  
Vol 52 (1-2) ◽  
pp. 83-84
Author(s):  
Marco Cardone ◽  
Anna Mason ◽  
Elena Riboldi ◽  
Charles A. Stewart ◽  
Franca Gerosa ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Human Monocyte ◽  
Beta Glucan ◽  
Cell Responses

scholarly journals Pathogens MenTORing Macrophages and Dendritic Cells: Manipulation of mTOR and Cellular Metabolism to Promote Immune Escape

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 161 ◽  
Author(s):  
Lonneke V. Nouwen ◽  
Bart Everts
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Amino Acid ◽  
Immune Responses ◽  
Metabolic Pathways ◽  
Immune Escape ◽  
Mammalian Target Of Rapamycin ◽  
Metabolic Reprogramming ◽  
First Line

Myeloid cells, including macrophages and dendritic cells, represent an important first line of defense against infections. Upon recognition of pathogens, these cells undergo a metabolic reprogramming that supports their activation and ability to respond to the invading pathogens. An important metabolic regulator of these cells is mammalian target of rapamycin (mTOR). During infection, pathogens use host metabolic pathways to scavenge host nutrients, as well as target metabolic pathways for subversion of the host immune response that together facilitate pathogen survival. Given the pivotal role of mTOR in controlling metabolism and DC and macrophage function, pathogens have evolved strategies to target this pathway to manipulate these cells. This review seeks to discuss the most recent insights into how pathogens target DC and macrophage metabolism to subvert potential deleterious immune responses against them, by focusing on the metabolic pathways that are known to regulate and to be regulated by mTOR signaling including amino acid, lipid and carbohydrate metabolism, and autophagy.

scholarly journals Emergence of MicroRNAs as Key Players in Cancer Cell Metabolism

2019 ◽  
Vol 65 (9) ◽  
pp. 1090-1101 ◽  
Author(s):  
Sugarniya Subramaniam ◽  
Varinder Jeet ◽  
Judith A Clements ◽  
Jennifer H Gunter ◽  
Jyotsna Batra
Keyword(s):  
Fatty Acid ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Novel Therapeutic

AbstractBACKGROUNDMetabolic reprogramming is a hallmark of cancer. MicroRNAs (miRNAs) have been found to regulate cancer metabolism by regulating genes involved in metabolic pathways. Understanding this layer of complexity could lead to the development of novel therapeutic approaches.CONTENTmiRNAs are noncoding RNAs that have been implicated as master regulators of gene expression. Studies have revealed the role of miRNAs in the metabolic reprogramming of tumor cells, with several miRNAs both positively and negatively regulating multiple metabolic genes. The tricarboxylic acid (TCA) cycle, aerobic glycolysis, de novo fatty acid synthesis, and altered autophagy allow tumor cells to survive under adverse conditions. In addition, major signaling molecules, hypoxia-inducible factor, phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin/phosphatase and tensin homolog, and insulin signaling pathways facilitate metabolic adaptation in tumor cells and are all regulated by miRNAs. Accumulating evidence suggests that miRNA mimics or inhibitors could be used to modulate the activity of miRNAs that drive tumor progression via altering their metabolism. Currently, several clinical trials investigating the role of miRNA-based therapy for cancer have been launched that may lead to novel therapeutic interventions in the future.SUMMARYIn this review, we summarize cancer-related metabolic pathways, including glycolysis, TCA cycle, pentose phosphate pathway, fatty acid metabolism, amino acid metabolism, and other metabolism-related oncogenic signaling pathways, and their regulation by miRNAs that are known to lead to tumorigenesis. Further, we discuss the current state of miRNA therapeutics in the clinic and their future potential.

Differential Role Of Dendritic Cell Subsets In Shaping T-Cell Responses To Respiratory Viruses

2014 ◽  
Vol 133 (2) ◽  
pp. AB284
Author(s):  
Meera Rani Gupta ◽  
Deepthi Kolli ◽  
Antonella Casola ◽  
Roberto P. Garofalo
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
T Cell Responses ◽  
Respiratory Viruses ◽  
Cell Responses ◽  
Dendritic Cell Subsets

scholarly journals Mitochondrial Carriers and Substrates Transport Network: A Lesson from Saccharomyces cerevisiae

2021 ◽  
Vol 22 (16) ◽  
pp. 8496
Author(s):  
Alessandra Ferramosca ◽  
Vincenzo Zara
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Metabolic Pathways ◽  
Environmental Changes ◽  
Human Cells ◽  
Metabolic Reprogramming ◽  
Model Organisms ◽  
Mitochondrial Carrier ◽  
Mitochondrial Carriers ◽  
Functional Connections

The yeast Saccharomyces cerevisiae is one of the most widely used model organisms for investigating various aspects of basic cellular functions that are conserved in human cells. This organism, as well as human cells, can modulate its metabolism in response to specific growth conditions, different environmental changes, and nutrient depletion. This adaptation results in a metabolic reprogramming of specific metabolic pathways. Mitochondrial carriers play a fundamental role in cellular metabolism, connecting mitochondrial with cytosolic reactions. By transporting substrates across the inner membrane of mitochondria, they contribute to many processes that are central to cellular function. The genome of Saccharomyces cerevisiae encodes 35 members of the mitochondrial carrier family, most of which have been functionally characterized. The aim of this review is to describe the role of the so far identified yeast mitochondrial carriers in cell metabolism, attempting to show the functional connections between substrates transport and specific metabolic pathways, such as oxidative phosphorylation, lipid metabolism, gluconeogenesis, and amino acids synthesis. Analysis of the literature reveals that these proteins transport substrates involved in the same metabolic pathway with a high degree of flexibility and coordination. The understanding of the role of mitochondrial carriers in yeast biology and metabolism could be useful for clarifying unexplored aspects related to the mitochondrial carrier network. Such knowledge will hopefully help in obtaining more insight into the molecular basis of human diseases.

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