scholarly journals The Role of Tumor Necrosis Factor in Manipulating the Immunological Response of Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Dipranjan Laha ◽  
Robert Grant ◽  
Prachi Mishra ◽  
Naris Nilubol
Keyword(s):  
Drug Delivery ◽  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Tumor Necrosis Factor ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Necrosis ◽  
Cancer Drug ◽  
Tnf Α ◽  
Necrosis Factor

The tumor microenvironment (TME) is an intricate system within solid neoplasms. In this review, we aim to provide an updated insight into the TME with a focus on the effects of tumor necrosis factor-α (TNF-α) on its various components and the use of TNF-α to improve the efficiency of drug delivery. The TME comprises the supporting structure of the tumor, such as its extracellular matrix and vasculature. In addition to cancer cells and cancer stem cells, the TME contains various other cell types, including pericytes, tumor-associated fibroblasts, smooth muscle cells, and immune cells. These cells produce signaling molecules such as growth factors, cytokines, hormones, and extracellular matrix proteins. This review summarizes the intricate balance between pro-oncogenic and tumor-suppressive functions that various non-tumor cells within the TME exert. We focused on the interaction between tumor cells and immune cells in the TME that plays an essential role in regulating the immune response, tumorigenesis, invasion, and metastasis. The multifunctional cytokine, TNF-α, plays essential roles in diverse cellular events within the TME. The uses of TNF-α in cancer treatment and to facilitate cancer drug delivery are discussed. The effects of TNF-α on tumor neovasculature and tumor interstitial fluid pressure that improve treatment efficacy are summarized.

scholarly journals The Role of TRAIL/DRs in the Modulation of Immune Cells and Responses

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1469 ◽  
Author(s):  
Duygu Sag ◽  
Zeynep Ozge Ayyildiz ◽  
Sinem Gunalp ◽  
Gerhard Wingender
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Necrosis Factor ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Necrosis ◽  
Death Receptors ◽  
Induction Of Apoptosis ◽  
Necrosis Factor

Expression of TRAIL (tumor necrosis factor–related apoptosis–inducing ligand) by immune cells can lead to the induction of apoptosis in tumor cells. However, it becomes increasingly clear that the interaction of TRAIL and its death receptors (DRs) can also directly impact immune cells and influence immune responses. Here, we review what is known about the role of TRAIL/DRs in immune cells and immune responses in general and in the tumor microenvironment in particular.

scholarly journals Inactive Rhomboid Protein 2 Mediates Intestinal Inflammation by Releasing Tumor Necrosis Factor–α

2019 ◽  
Vol 26 (2) ◽  
pp. 242-253
Author(s):  
Jee Hyun Kim ◽  
Sung Wook Hwang ◽  
Jaemoon Koh ◽  
Jaeyoung Chun ◽  
Changhyun Lee ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Immune Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Intestinal Inflammation ◽  
Converting Enzyme ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Inactive rhomboid 2 (iRhom2) is an essential molecule required for the maturation of tumor necrosis factor–α–converting enzyme in immune cells, which regulates TNF-α release. The aim of this study was to investigate the role of iRhom2 in intestinal inflammation.

Endotoxin, tumor necrosis factor, and dexamethasone effects on human endothelial cell fibronectin dynamics: synthesis, matrix assembly, and receptor expression

1995 ◽  
Vol 73 (7-8) ◽  
pp. 515-524 ◽  
Author(s):  
Lewis H. Romer ◽  
Richard A. Polin
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Receptor Expression ◽  
Matrix Assembly ◽  
Down Regulation ◽  
Cell Extracts ◽  
Tnf Α ◽  
Necrosis Factor

The three inflammatory modulators endotoxin, tumor necrosis factor (TNF) α, and dexamethasone (DEX) were studied for their effects on fibronectin (FN) dynamics in human umbilical vein endothelial cells. Cell culture supernatants were analyzed for new soluble pool FN synthesis. Endotoxin (LPS) (10 μg/mL) decreased the newly synthesized soluble pool of FN (p < 0.05). An increase in soluble FN was demonstrated with 1 and 10 ng/mL TNF α (p < 0.05). DEX decreased newly synthesized endothelial cell (EC) FN in the soluble pool at 4, 40, and 400 μg/mL (p < 0.05). Extracellular matrix FN content was examined using immunofluorescence. The thick FN mesh seen in control cells contrasted with a decreased FN matrix after treatment with each of the three study agents. Immunoprecipitation of the FN receptor α5β1 integrin from [35S]methionine-labelled cell extracts demonstrated down regulation of receptor expression by both TNF α and DEX as compared with control samples. These data indicate that LPS, TNF α, and DEX may weaken EC–substratum adhesion by differential effects on FN synthesis and secretion, FN incorporation into the extracellular matrix, and down regulation of FN receptor expression.Key words: endothelium, fibronectin, extracellular matrix, integrin, cytokine.

scholarly journals Plasma Levels of Matrix Metalloproteinase (MMP)-2, MMP-9 and Tumor Necrosis Factor-α in Chronic Hepatitis C Virus Patients

2015 ◽  
Vol 9 (1) ◽  
pp. 136-140 ◽  
Author(s):  
Mohamed S Abdel-Latif
Keyword(s):  
Extracellular Matrix ◽  
Tumor Necrosis Factor ◽  
Liver Fibrosis ◽  
Plasma Levels ◽  
Tumor Necrosis ◽  
Cirrhotic Liver ◽  
Control Group ◽  
Tnf Α ◽  
Chronic Hcv ◽  
Necrosis Factor

Background: In chronic HCV infection, pathological accumulation of the extracellular matrix is the main feature of liver fibrosis; that indicates the imbalanced rate of increased matrix synthesis to decreased breakdown of connective tissue proteins. Matrix metalloproteinases (MMPs) play a crucial role in remodeling of extracellular matrix. It is known that expression of MMPs is regulated by Tumor necrosis factor (TNF)-α. Also, levels of TNF-α in liver and serum are increased in chronic HCV patient. Accordingly, this study aimed to correlate the plasma levels of MMP-2, MMP-9 and TNF-α in chronic HCV patients with the pathogenesis of the liver. Methods: The current study was conducted on 15 fibrotic liver cases with detectable HCV RNA, 10 HCV cirrhotic liver cases, and 15 control subjects of matched age and sex. Plasma MMP-2, MMP-9 and TNF-α were measured by ELISA. Results: Data revealed that the MMP2, MMP9 and TNF-α levels showed a significant elevation in chronic HCV patients compared to control group (p= 0.001). But, no significant correlation was observed in levels of MMP-2, MMP-9, and TNF-α between fibrotic and cirrhotic cases. Conclusions: MMP-2, MMP-9 and TNF-α showed high reproducibility to differentiate chronic HCV patients from control group. On the contrary, MMP-2, MMP-9 and TNF-α were not able to differentiate fibrotic from cirrhotic liver cases. Thus, MMP-2, MMP-9 and TNF-α could not be correlated with the progression of liver disease. Rather they could be used as prognostic markers of liver fibrosis.

scholarly journals Preparation of agarose-glucan for anti-tumor necrosis factor protein drug delivery

2018 ◽  
Vol 34 (4) ◽  
Author(s):  
Hường Pham
Keyword(s):  
Drug Delivery ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Liquid Paraffin ◽  
Protein Drug ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Model Protein ◽  
Protein Drug Delivery ◽  
Necrosis Factor

Our purpose was to develop and characterize a protein drug delivery system in agarose-glucan complex. The complex was produced by sonicating the mixture of agarose-glucan components and a protein in liquid paraffin with Sonics Vibracell Processor adapted from method of Nuo Wang et all 1997 [1]. We used etanercept, an anti-tumor necrosis factor-alpha (TNF-α) as a model protein drug, which was encapsulated successfully into agarose-glucan complex system. This protein can neutralize the TNF-α, a pro-inflammatory cytokines that plays a pivotal role in regulating the inflammatory response in rheumatoid arthritis (RA) and well known as mediator worsening RA pathogenesis. The agarose-glucan complex we made possessed a range of sizes from 30 to 150 nm, dissolving well within a range of pH buffer from 5.2 to 6.2, an average protein encapsulated efficiency up to 70%, and protein release efficiency of 50% after 24 hours. This research is the base for developing nanogel-size targeted drug delivery in RA treatment.

scholarly journals TRAIL-based gene delivery and therapeutic strategies

2019 ◽  
Vol 40 (11) ◽  
pp. 1373-1385 ◽  
Author(s):  
Hui-hai Zhong ◽  
Hui-yuan Wang ◽  
Jian Li ◽  
Yong-zhuo Huang
Keyword(s):  
Tumor Necrosis Factor ◽  
Gene Delivery ◽  
Tumor Cells ◽  
Tumor Necrosis ◽  
Viral Vectors ◽  
Bystander Effect ◽  
Gene Transfection ◽  
Cancer Drug ◽  
Drug Candidate ◽  
Necrosis Factor

Abstract TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also known as APO2L, belongs to the tumor necrosis factor family. By binding to the death receptor 4 (DR4) or DR5, TRAIL induces apoptosis of tumor cells without causing side toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great attention for its promise of serving as a cancer drug candidate. However, the treatment efficacy of TRAIL protein was under expectation in the clinical trials because of the short half-life and the resistance of cancer cells. TRAIL gene transfection can produce a “bystander effect” of tumor cell killing and provide a potential solution to TRAIL-based cancer therapy. In this review we focus on TRAIL gene therapy and various design strategies of TRAIL DNA delivery including non-viral vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. The opportunities and challenges of TRAIL-based gene delivery and therapy are discussed.

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