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Toll like receptors and cancer

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https://www.readbyqxmd.com/read/29670922/clinicopathological-features-and-increased-expression-of-toll-like-receptor-4-of-gastric-cardia-cancer-in-a-high-risk-chinese-population
#1
Guangcan Chen, Muming Xu, Jingyao Chen, Liangli Hong, Wenting Lin, Shukun Zhao, Guohong Zhang, Guo Dan, Shuhui Liu
The incidence of gastric cardia cancer (GCC) is high in China. However, the clinicopathological characteristics and the carcinogenesis of GCC are unclear. Toll-like receptor 4 (TLR4) is an important innate immunity receptor and has a role in non-GCC (NGCC). We compared the clinicopathological characteristics of GCC patients from a high-risk area in China to esophageal cancer (EC) patients. Immunohistochemistry for TLR4 was performed in 201 histological samples of normal gastric cardia mucosa ( n = 11), gastric cardia inflammation ( n = 87), and GCC ( n = 103)...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29667229/uc-1v150-a-potent-tlr7-agonist-capable-of-activating-macrophages-and-potentiating-mab-mediated-target-cell-deletion
#2
Lekh N Dahal, Adam Gadd, Alexander D Edwards, Mark S Cragg, Stephen A Beers
Toll like receptors (TLR) are critical mediators of the immune system with their activation linked to infection, inflammation and the pathogenesis of immune diseases including autoimmunity and cancer. For this reason, over the last two decades, TLR and their associated signalling pathways have been targeted therapeutically to enhance innate and adaptive immunity. Several TLR ligands, both endogenous and synthetic are at various phases of clinical testing, and new ligands are continually emerging. Agonists of TLR7 are known immune response modifiers, simultaneously stimulating several cell types, resulting in immune cell activation and cytokine and chemokine release...
April 18, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29663503/mir-135a-represses-oxidative-stress-and-vascular-inflammatory-events-via-targeting-toll-like-receptor-4-in-atherogenesis
#3
Xian-Jin Du, Jing-Min Lu
Plenty of microRNAs have been identified as critical mediators in atherosclerosis progression, which is still a great threat to human health. Oxidative stress and inflammation have been implicated to contribute a lot to atherosclerosis development. MiR-135a is abnormally expressed in various cancer types, however its function in atherosclerosis is largely unexplored. Ox-LDL is commonly recognized as a crucial atherosclerosis regulator. In our current study, we observed ox-LDL was able to induce RAW264.7 cell apoptosis and meanwhile miR-135a was restrained by ox-LDL both dose-dependently and time- dependently...
April 16, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29662615/transcriptome-and-proteome-profiling-reveals-stress-induced-expression-signatures-of-imiquimod-treated-tasmanian-devil-facial-tumor-disease-dftd-cells
#4
Amanda L Patchett, Richard Wilson, Jac C Charlesworth, Lynn M Corcoran, Anthony T Papenfuss, Bruce A Lyons, Gregory M Woods, Cesar Tovar
As a topical cancer immunotherapy, the toll-like receptor 7 ligand imiquimod activates tumor regression via stimulation of immune cell infiltration and cytotoxic responses. Imiquimod also exerts direct pro-apoptotic effects on tumor cells in vitro , but a role for these effects in imiquimod-induced tumor regression remains undefined. We previously demonstrated that cell lines derived from devil facial tumor disease (DFTD), a transmissible cancer threatening the survival of the Tasmanian devil ( Sarcophilus harrisii ), are sensitive to imiquimod-induced apoptosis...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661854/targeting-toll-like-receptors-in-cancer-prevention
#5
EDITORIAL
Karen S Sfanos
There is a pressing need for the development of new prevention strategies for the most common worldwide malignancy, nonmelanoma skin cancer (NMSC), as sun protection efforts have not proven to be completely effective. Interestingly, despite the known circumstance that individuals undergoing chronic immunosuppression are at a substantially increased risk for developing NMSC, in this issue of Cancer Prevention Research , Blohm-Mangone and colleagues provide new evidence that topical application of the Toll-like receptor 4 (TLR4) antagonist resatorvid may be efficacious as a chemopreventive agent in NMSC specifically via blocking UV-induced inflammatory signaling...
April 16, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29656235/effective-cancer-immunotherapy-in-mice-by-polyic-imiquimod-complexes-and-engineered-magnetic-nanoparticles
#6
Ana Isabel Bocanegra Gondan, Ane Ruiz-de-Angulo, Aintzane Zabaleta, Nina Gómez Blanco, Beatriz Macarena Cobaleda-Siles, María Jesús García-Granda, Daniel Padro, Jordi Llop, Blanca Arnaiz, María Gato, David Escors, Juan C Mareque-Rivas
Encouraging results are emerging from systems that exploit Toll like receptor (TLR) signaling, nanotechnology, checkpoint inhibition and molecular imaging for cancer immunotherapy. A major remaining challenge is developing effective, durable and tumour-specific immune responses without systemic toxicity. Here, we report a simple and versatile system based on synergistic activation of immune responses and direct cancer cell killing by combined TLR ligation using polyIC as TLR3 and imiquimod (R837) as TLR7 agonist, in combination with the model antigen ovalbumin (OVA) and phospholipid micelles loaded with zinc-doped iron oxide magnetic nanoparticles (MNPs)...
April 3, 2018: Biomaterials
https://www.readbyqxmd.com/read/29628795/the-revival-of-cpg-oligonucleotide-based-cancer-immunotherapies
#7
REVIEW
Tomasz Adamus, Marcin Kortylewski
The promising results of clinical trials using immune checkpoint inhibitors revived interests in cancer immunotherapy. However, it also became apparent that efficacy of immune checkpoint blockade can benefit from combining it with immunostimulatory strategies. Here, we review prior and re-emerging approaches using Toll-like Receptor 9 (TLR9) agonists, CpG oligodeoxynucleotides (ODNs), focused on the generation of antitumor immune responses in cancer patients. While numerous early clinical trials using TLR9 ligands in monotherapies provided evidence of CpG ODNs tolerability and safety, they failed to demonstrate sufficient antitumor efficacy...
March 2018: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/29621153/linkage-of-infection-to-adverse-systemic-complications-periodontal-disease-toll-like-receptors-and-other-pattern-recognition-systems
#8
REVIEW
Shannon M Wallet, Vishwajeet Puri, Frank C Gibson
Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) that provide innate immune sensing of conserved pathogen-associated molecular patterns (PAMPs) to engage early immune recognition of bacteria, viruses, and protozoa. Furthermore, TLRs provide a conduit for initiation of non-infectious inflammation following the sensing of danger-associated molecular patterns (DAMPs) generated as a consequence of cellular injury. Due to their essential role as DAMP and PAMP sensors, TLR signaling also contributes importantly to several systemic diseases including cardiovascular disease, diabetes, and others...
April 5, 2018: Vaccines
https://www.readbyqxmd.com/read/29606147/baseline-antibody-profiles-predict-toxicity-in-melanoma-patients-treated-with-immune-checkpoint-inhibitors
#9
Michael F Gowen, Keith M Giles, Danny Simpson, Jeremy Tchack, Hua Zhou, Una Moran, Zarmeena Dawood, Anna C Pavlick, Shaohui Hu, Melissa A Wilson, Hua Zhong, Michelle Krogsgaard, Tomas Kirchhoff, Iman Osman
BACKGROUND: Immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1, or the combination) enhance anti-tumor immune responses, yielding durable clinical benefit in several cancer types, including melanoma. However, a subset of patients experience immune-related adverse events (irAEs), which can be severe and result in treatment termination. To date, no biomarker exists that can predict development of irAEs. METHODS: We hypothesized that pre-treatment antibody profiles identify a subset of patients who possess a sub-clinical autoimmune phenotype that predisposes them to develop severe irAEs following immune system disinhibition...
April 2, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29602239/inflammatory-factor-receptor-toll-like-receptor-4-controls-telomeres-through-heterochromatin-protein-1-isoforms-in-liver-cancer-stem-cell
#10
Qidi Zheng, Jie Xu, Zhuojia Lin, Yanan Lu, Xiaoru Xin, Xiaonan Li, Yuxin Yang, Qiuyu Meng, Chen Wang, Wujun Xiong, Dongdong Lu
Toll-like receptor 4 (TLR4) which acts as a receptor for lipopolysaccharide (LPS) has been reported to be involved in carcinogenesis. However, the regulatory mechanism of it has not been elucidated. Herein, we demonstrate that TLR4 promotes the malignant growth of liver cancer stem cells. Mechanistically, TLR4 promotes the expression of histone-lysine N-methyltransferase (SUV39 h2) and increases the formation of trimethyl histone H3 lysine 9-heterochromatin protein 1-telomere repeat binding factor 2 (H3K9me3-HP1-TRF2) complex at the telomeric locus under mediation by long non coding RNA urothelial cancer-associated 1 (CUDR)...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29601492/obesity-inflammation-toll-like-receptor-4-and-fatty-acids
#11
REVIEW
Marcelo Macedo Rogero, Philip C Calder
Obesity leads to an inflammatory condition that is directly involved in the etiology of cardiovascular diseases, type 2 diabetes mellitus, and certain types of cancer. The classic inflammatory response is an acute reaction to infections or to tissue injuries, and it tends to move towards resolution and homeostasis. However, the inflammatory process that was observed in individuals affected by obesity and metabolic syndrome differs from the classical inflammatory response in certain respects. This inflammatory process manifests itself systemically and it is characterized by a chronic low-intensity reaction...
March 30, 2018: Nutrients
https://www.readbyqxmd.com/read/29596890/immuno-modulators-enhance-antigen-specific-immunity-and-anti-tumor-effects-of-mesothelin-specific-chimeric-dna-vaccine-through-promoting-dc-maturation
#12
Yu-Li Chen, Ming-Cheng Chang, Ying-Cheng Chiang, Han-Wei Lin, Nai-Yun Sun, Chi-An Chen, Wei-Zen Sun, Wen-Fang Cheng
As a tumor antigen, mesothelin (MSLN) can be identified in various malignancies. MSLN is potential for antigen-specific cancer vaccines. We generated a novel chimeric DNA vaccine using antigen-specific connective tissue growth factor lined with MSLN (CTGF/MSLN). The anti-tumor effects of the CTGF/MSLN DNA vaccine combined with anti-CD40 Ab and toll-like receptor 3 ligand-poly(I:C) were validated in an MSLN-expressing model. CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice demonstrated potent anti-tumor effects with longer survival and less tumor volumes...
March 26, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29595418/human-papillomavirus-hpv-16-e6-oncoprotein-targets-the-toll-like-receptor-pathway
#13
Lucas Boeno Oliveira, Ismar R Haga, Luisa Lina Villa
Cervical cancer is one of the leading causes of death in women worldwide and is etiologically linked to human papillomavirus (HPV) infection. Viral early proteins E6 and E7 manipulate cellular functions to promote the virus life cycle and are essential to the cellular transformation process. The innate immune system plays a pivotal role in the natural history of HPV infection. Among the various proteins that mediate the innate immune response, Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and initiate the immune response...
March 29, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29589540/-lactoferrin-and-peptide-derivatives-antimicrobial-agents-with-potential-use-in-nonspecific-immunity-modulation
#14
Maria Elisa Drago-Serrano, Rafael Campos-Rodriguez, Julio Cesar Carrero, Mireya de la Garza
Lactoferrin (Lf) is a conserved cationic non-heme glycoprotein that is part of the innate immune defense system of mammals. Lf is present in colostrum, milk and mucosal sites, and it is also produced by polymorphonuclear neutrophils and secreted at infection sites. Lf and Lf N-terminus peptide-derivatives named lactoferricins (Lfcins) are molecules with microbiostatic and microbicidal action in a wide array of pathogens. In addition, they display regulatory properties on components of nonspecific immunity, including toll-like receptors, pro- and anti-inflammatory cytokines, and reactive oxygen species...
March 27, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29588627/zymosan-attenuates-melanoma-growth-progression-increases-splenocyte-proliferation-and-induces-tlr-2-4-and-tnf-%C3%AE-expression-in-mice
#15
Mehdi Taghavi, Esmaeil Mortaz, Alireza Khosravi, Ghasem Vahedi, Gert Folkerts, Mohammad Varahram, Mehdi Kazempour-Dizaji, Johan Garssen, Ian M Adcock
Background: Melanoma is one of the most common types of skin malignancies. Since current therapies are suboptimal, considerable interest has focused on novel natural-based treatments. Toll-like receptors (TLRs) play an important role in evoking innate immunity against cancer cells. Zymosan, a known TLR-2 agonist, is a glucan derived from yeast cell walls with promising immunomodulatory effects. The aim of this study was to evaluate whether Saccharomyces cerevisiae -derived zymosan-modulated skin melanoma progression by regulation of TLR-2 and TLR-4 expression in peritoneal macrophages and serum TNF-α level...
2018: Journal of Inflammation
https://www.readbyqxmd.com/read/29581525/innate-immune-system-activation-in-zebrafish-and-cellular-models-of-diamond-blackfan-anemia
#16
Nadia Danilova, Mark Wilkes, Elena Bibikova, Min-Young Youn, Kathleen M Sakamoto, Shuo Lin
Deficiency of ribosomal proteins (RPs) leads to Diamond Blackfan Anemia (DBA) associated with anemia, congenital defects, and cancer. While p53 activation is responsible for many features of DBA, the role of immune system is less defined. The Innate immune system can be activated by endogenous nucleic acids from non-processed pre-rRNAs, DNA damage, and apoptosis that occurs in DBA. Recognition by toll like receptors (TLRs) and Mda5-like sensors induces interferons (IFNs) and inflammation. Dying cells can also activate complement system...
March 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29568370/gram-negative-bacteria-facilitate-tumor-progression-through-tlr4-il-33-pathway-in-patients-with-non-small-cell-lung-cancer
#17
Mengyao Sun, Yang Bai, Song Zhao, Xiyu Liu, Yongsheng Gao, Lei Wang, Bin Liu, Dashi Ma, Chunye Ma
Non-small-cell lung cancer (NSCLC) accounts for the most cases in clinical lung cancer patients. Patients with NSCLC are often diagnosed in advanced stage and frequently infected with gram-negative bacteria. Pulmonary infection with gram-negative bacteria is the most frequent postoperative complication in NSCLC patients. While accumulating evidence indicate an involvement of gram-negative bacteria in NSCLC progression, the underlying mechanisms remain largely unknown. Herein, we explored the effect of gram-negative bacteria on tumor progression using tumor cells from NSCLC patients...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29567829/the-pancreatic-cancer-microbiome-promotes-oncogenesis-by-induction-of-innate-and-adaptive-immune-suppression
#18
Smruti Pushalkar, Mautin Hundeyin, Donnele Daley, Constantinos P Zambirinis, Emma Kurz, Ankita Mishra, Navyatha Mohan, Berk Aykut, Mykhaylo Usyk, Luisana E Torres, Gregor Werba, Kevin Zhang, Yuqi Guo, Qianhao Li, Neha Akkad, Sarah Lall, Benjamin Wadowski, Johana Gutierrez, Juan Andres Kochen Rossi, Jeremy W Herzog, Brian Diskin, Alejandro Torres-Hernandez, Josh Leinwand, Wei Wang, Pardeep S Taunk, Shivraj Savadkar, Malvin Janal, Anjana Saxena, Xin Li, Deirdre Cohen, R Balfour Sartor, Deepak Saxena, George Miller
We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4+ T cells and CD8+ T-cell activation...
March 22, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29566186/meat-and-fiber-intake-and-interaction-with-pattern-recognition-receptors-tlr1-tlr2-tlr4-and-tlr10-in-relation-to-colorectal-cancer-in-a-danish-prospective-case-cohort-study
#19
Tine Iskov Kopp, Ulla Vogel, Anne Tjonneland, Vibeke Andersen
Background: Meat and dietary fiber are associated with increased and decreased risk of colorectal cancer (CRC), respectively. Toll-like receptors (TLRs) regulate the intestinal immune response in a complex interplay between the mucosal epithelium and the microbiota and may therefore be important modulators of diet-induced CRC together with other inflammatory mediators. Objective: Our aim was to investigate the association between functional TLR polymorphisms and risk of CRC and the interaction with dietary factors...
March 1, 2018: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29563317/extended-release-of-perioperative-immunotherapy-prevents-tumor-recurrence-and-eliminates-metastases
#20
Chun Gwon Park, Christina A Hartl, Daniela Schmid, Ellese M Carmona, Hye-Jung Kim, Michael S Goldberg
Cancer immunotherapy can confer durable benefit, but the percentage of patients who respond to this approach remains modest. The ability to concentrate immunostimulatory compounds at the site of disease can overcome local immune tolerance and reduce systemic toxicity. Surgical resection of tumors may improve the efficacy of immunotherapy by removing the concentrated immunosuppressive microenvironment; however, it also removes tumor-specific leukocytes as well as tumor antigens that may be important to establishing antitumor immunity...
March 21, 2018: Science Translational Medicine
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