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Toll like receptors and cancer

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https://www.readbyqxmd.com/read/28815730/loss-of-bmi-1-dampens-migration-and-emt-of-colorectal-cancer-in-inflammatory-microenvironment-through-tlr4-md-2-myd88-mediated-nf-%C3%AE%C2%BAb-signaling
#1
Kai Ye, Qi-Wei Chen, Ya-Feng Sun, Jian-An Lin, Jian-Hua Xu
Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment created by immune cells facilitates tumor migration. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in an inflammatory microenvironment. B-lymphoma Moloney murine leukemia virus insertion region 1 (BMI-1) acts as an oncogene in various tumors. Ectopic expression of Bmi-1 have an effect on EMT and invasiveness. The purpose of this study was to investigate the efficacy of BMI-1 on inflammation-induced tumor migration and EMT and the underlying mechanism...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28811970/trial-watch-dendritic-cell-based-anticancer-immunotherapy
#2
REVIEW
Abhishek D Garg, Monica Vara Perez, Marco Schaaf, Patrizia Agostinis, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called "maturation cocktail" (typically a combination of pro-inflammatory cytokines and Toll-like receptor agonists), followed by DC reintroduction into patients. DC vaccines have been documented to (re)activate tumor-specific T cells in both preclinical and clinical settings...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811960/rehmannia-glutinosa-polysaccharide-induces-toll-like-receptor-4-dependent-spleen-dendritic-cell-maturation-and-anti-cancer-immunity
#3
Li Xu, Minseok Kwak, Wei Zhang, Ling Zeng, Peter Chang-Whan Lee, Jun-O Jin
Rehmannia glutinosa polysaccharide (RGP) has shown an activation of immune cells in vitro. However, the immune stimulatory effect of RGP in a mouse in vivo is not well studied. In this study, we examined the effect of RGP on dendritic cell (DC) activation and anticancer immunity in vivo. Treatments of RGP in C56BL/6 mice induced increased levels of co-stimulatory molecule expression and pro-inflammatory cytokine production in spleen DCs dependent on toll-like receptor 4 (TLR4), and those DCs promoted interferon-gamma (IFNγ) production in CD4(+) and CD8(+) T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28808017/antitumor-effect-of-batf2-through-il-12-p40-up-regulation-in-tumor-associated-macrophages
#4
Hisashi Kanemaru, Fumihiro Yamane, Kiyoharu Fukushima, Takanori Matsuki, Takahiro Kawasaki, Isao Ebina, Kanako Kuniyoshi, Hiroki Tanaka, Kenta Maruyama, Kazuhiko Maeda, Takashi Satoh, Shizuo Akira
The development of effective treatments against cancers is urgently needed, and the accumulation of CD8(+) T cells within tumors is especially important for cancer prognosis. Although their mechanisms are still largely unknown, growing evidence has indicated that innate immune cells have important effects on cancer progression through the production of various cytokines. Here, we found that basic leucine zipper transcription factor ATF-like 2 (Batf2) has an antitumor effect. An s.c. inoculated tumor model produced fewer IL-12 p40(+) macrophages and activated CD8(+) T cells within the tumors of Batf2(-/-) mice compared with WT mice...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28794879/human-papillomavirus-driven-immune-deviation-challenge-and-novel-opportunity-for-immunotherapy
#5
REVIEW
Sigrun Smola, Connie Trimble, Peter L Stern
It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer...
June 2017: Therapeutic Advances in Vaccines
https://www.readbyqxmd.com/read/28790196/trif-dependent-toll-like-receptor-signaling-suppresses-scd1-transcription-in-hepatocytes-and-prevents-diet-induced-hepatic-steatosis
#6
Jing Chen, Jin Li, Jensen H C Yiu, Jenny K W Lam, Chi-Ming Wong, Bernhard Dorweiler, Aimin Xu, Connie W Woo
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that ranges in severity from hepatic steatosis to steatohepatitis, the latter of which is a major predisposing factor for liver cirrhosis and cancer. Toll-like receptor (TLR) signaling, which is critical for innate immunity, is generally believed to aggravate disease progression by inducing inflammation. Unexpectedly, we found that deficiency in TIR domain-containing adaptor-inducing interferon-β (TRIF), a cytosolic adaptor that transduces some TLR signals, worsened hepatic steatosis induced by a high-fat diet (HFD) and that such exacerbation was independent of myeloid cells...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28778074/toll-like-receptor-expression-in-human-non-small-cell-lung-carcinoma-potential-prognostic-indicators-of-disease
#7
Alison K Bauer, Brad L Upham, Elizabeth A Rondini, Meredith A Tennis, Kalpana Velmuragan, David Wiese
INTRODUCTION: Lung cancer remains the highest cause of cancer mortality worldwide. Toll-like receptors (TLR) are innate immune receptors that have both pro- and anti-tumorigenic properties. Based on findings from epidemiological studies and in rodents, we hypothesized that elevated TLR expression would be a positive prognostic indicator of disease in non-small cell lung carcinoma patients. RESULTS: Higher mRNA expression of TLR1-3 and 5-8 were significantly associated with increased overall survival (OS) when analyzed individually or as a group in both non-small cell lung carcinoma (NSCLC) patients and in the adenocarcinoma (ADC) subtype...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28771725/tlr4-and-nf%C3%AE%C2%BAb-signaling-is-critical-for-taxol-resistance-in-ovarian-carcinoma-cells
#8
Nian-Kang Sun, Shang-Lang Huang, Ting-Chang Chang, Chuck C-K Chao
We report here that toll-like receptor 4 (TLR4) and ABCB1 are upregulated in SKOV3 ovarian carcinoma cells that acquired resistance to the anticancer drug taxol. Silencing of TLR4 using short-hairpin RNA sensitized taxol-resistant SKOV3 cells to taxol (4.6 fold), whereas ectopic expression of TLR4 in parental, taxol-sensitive SKOV3 cells or TLR4-null HEK293 cells induced taxol resistance (∼2 fold). A sub-lethal dose of taxol induced ABCB1 protein expression in taxol-resistant SKOV3 cells. Inactivation of TLR4 using chemical inhibitors (CLI-095 and AO-I) downregulated ABCB1 protein expression and enhanced the cytotoxic activity of taxol in taxol-resistant SKOV3 cells...
August 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28766672/seabuckthorn-berry-polysaccharide-protects-against-carbon-tetrachloride-induced-hepatotoxicity-in-mice-via-anti-oxidative-and-anti-inflammatory-activities
#9
Wei Zhang, Xiaohui Zhang, Kai Zou, Jiming Xie, Shimin Zhao, Jingran Liu, Huan Liu, Jinling Wang, Yuzhen Wang
The berries of Seabuckthorn (Hippophae rhamnoides L.) are traditional medicinal foods that have been used by Tibetans and Mongolians for thousands of years. The polysaccharides are the main components of Seabuckthorn berries, possessing immune stimulating, anti-cancer and anti-fatigue activities. The present study focused on evaluating the protective effects and mechanisms of Seabuckthorn berry polysaccharide (SP) against carbon tetrachloride (CCl4)-induced hepatotoxicity. Mice were orally administrated with 50, 100 and 200 mg kg(-1) of SP once daily for 14 consecutive days prior to CCl4 challenge...
August 2, 2017: Food & Function
https://www.readbyqxmd.com/read/28766555/the-tlr9-agonist-mgn1703-triggers-a-potent-type-i-interferon-response-in-the-sigmoid-colon
#10
A R Krarup, M Abdel-Mohsen, M H Schleimann, L Vibholm, P A Engen, A Dige, B Wittig, M Schmidt, S J Green, A Naqib, A Keshavarzian, X Deng, R Olesen, A M Petersen, T Benfield, L Østergaard, T A Rasmussen, J Agnholt, J R Nyengaard, A Landay, O S Søgaard, S K Pillai, M Tolstrup, P W Denton
Toll-like receptor 9 (TLR9) agonists are being developed for treatment of colorectal and other cancers, yet the impact of these drugs on human intestines remains unknown. This, together with the fact that there are additional potential indications for TLR9 agonist therapy (e.g., autoimmune and infectious diseases), led us to investigate the impact of MGN1703 (Lefitolimod) on intestinal homeostasis and viral persistence in HIV-positive individuals. Colonic sigmoid biopsies were collected (baseline and week four) from 11 HIV+ individuals on suppressive antiretroviral therapy, who received MGN1703 (60 mg s...
August 2, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28765705/divergent-expression-of-bacterial-wall-sensing-toll-like-receptors-2-and-4-in-colorectal-cancer
#11
Karoliina Paarnio, Sara Väyrynen, Kai Klintrup, Pasi Ohtonen, Markus J Mäkinen, Jyrki Mäkelä, Tuomo J Karttunen
AIM: To characterize the expression of toll-like receptors (TLR) 2 and 4 in colorectal cancer (CRC) and in normal colorectal mucosa. METHODS: We analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present...
July 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28758266/a-ph-sensitive-macromolecular-prodrug-as-tlr7-8-targeting-immune-response-modifier
#12
Stefan Aichhorn, Anne Linhardt, Angela Halfmann, Markus Nadlinger, Stefanie Kirchberger, Manuela Stadler, Barbara Dillinger, Martin Distel, Alexander Dohnal, Ian Teasdale, Wolfgang Schoefberger
The chemical synthesis and biological activity of novel functionalized imidazoquinoline derivatives to generate Toll-like receptor 7/8 specific prodrugs are presented. In vivo activity of ImQs to induce inflammation was confirmed in zebrafish larvae. After covalent ligation to fully biodegradable polyphosphazenes, the macromolecular prodrugs were designed to undergo intracellular pH-sensitive release of ImQs to induce inflammation through binding to endosomal TLR7/8. We showed ImQ dissociation from prodrugs at a pH 5 pointing towards endosomal prodrug degradability...
July 30, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28754746/tumor-derived-exosomes-modulate-pd-l1-expression-in-monocytes
#13
Franziska Haderk, Ralph Schulz, Murat Iskar, Laura Llaó Cid, Thomas Worst, Karolin V Willmund, Angela Schulz, Uwe Warnken, Jana Seiler, Axel Benner, Michelle Nessling, Thorsten Zenz, Maria Göbel, Jan Dürig, Sven Diederichs, Jérôme Paggetti, Etienne Moussay, Stephan Stilgenbauer, Marc Zapatka, Peter Lichter, Martina Seiffert
In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell-derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples...
July 28, 2017: Science Immunology
https://www.readbyqxmd.com/read/28753429/fusobacterium-nucleatum-promotes-chemoresistance-to-colorectal-cancer-by-modulating-autophagy
#14
TaChung Yu, Fangfang Guo, Yanan Yu, Tiantian Sun, Dan Ma, Jixuan Han, Yun Qian, Ilona Kryczek, Danfeng Sun, Nisha Nagarsheth, Yingxuan Chen, Haoyan Chen, Jie Hong, Weiping Zou, Jing-Yuan Fang
Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F...
July 27, 2017: Cell
https://www.readbyqxmd.com/read/28751891/deconvolution-of-the-response-to-bacillus-calmette-gu%C3%A3-rin-reveals-nf-%C3%AE%C2%BAb-induced-cytokines-as-autocrine-mediators-of-innate-immunity
#15
Aurélie Bisiaux, Jeremy Boussier, Darragh Duffy, Lluis Quintana-Murci, Magnus Fontes, Matthew L Albert
Bacillus Calmette-Guérin (BCG) is used as a vaccine and diagnostic test for tuberculosis, as well as immunotherapy in the treatment of bladder cancer. While clinically useful, the response to mycobacterial stimulation is complex and the induced protein signature remains poorly defined. We characterized the cell types directly engaged by BCG, as well as the induced cytokine loops that transmit signal(s) to bystander cells. Standardized whole-blood stimulations and mechanistic studies on single and purified cell populations identified distinct patterns of activation in monocytes as compared to neutrophils and invariant lymphocyte populations...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28746799/lack-of-il-6-in-the-tumor-microenvironment-augments-type-1-immunity-and-increases-the-efficacy-of-cancer-immunotherapy
#16
Yosuke Ohno, Yujiro Toyoshima, Hideaki Yurino, Norikazu Monma, Huihui Xiang, Kentaro Sumida, Shun Kaneumi, Satoshi Terada, Shinichi Hashimoto, Kazuho Ikeo, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura
Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic cytokine, is produced in the tumor-bearing state. In this study, we investigated the precise effects of IL-6 on antitumor immunity and the subsequent tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild-type and IL-6-deficient mice. As a result, we found that tumor growth was decreased significantly in IL-6-deficient mice compared with wild-type mice and the reduction was abrogated by depletion of CD8(+) T cells...
July 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28744288/naltrexone-inhibits-il-6-and-tnf%C3%AE-production-in-human-immune-cell-subsets-following-stimulation-with-ligands-for-intracellular-toll-like-receptors
#17
Rachel Cant, Angus G Dalgleish, Rachel L Allen
The opioid antagonist naltrexone hydrochloride has been suggested to be a potential therapy at low dosage for multiple inflammatory conditions and cancers. Little is known about the immune-modulating effects of naltrexone, but an effect on the activity of toll-like receptor 4 (TLR4) has been reported. We analyzed the effects of naltrexone hydrochloride on IL-6 secretion by peripheral blood mononuclear cells (PBMC) in vitro following stimulation with ligands for TLR4 and for the intracellular receptors TLR7, TLR8, and TLR9...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28742407/tlr5-polymorphisms-rs2072493-rs5744174-and-rs5744168-are-not-genetic-risk-factors-for-chronic-helicobacter-pylori-infection-in-indian-tamils
#18
Vaishnavi Goda, Megala Jayaraman, Rekha Loganathan, Mehnaz Nazeer, Mohammed Ali, Premkumar Karunakaran, Panneer Devaraju
The incidence of Helicobacter pylori (H. pylori) infection and gastric cancer is on the rise in India, and the genetic factors influencing the increased susceptibility in Indian population remain obscure. Toll-like receptors (TLRs) play a major role in innate immune system and genetic polymorphisms affecting their function were reported to enhance the risk for H. pylori infection. Seventy-seven patients (n = 77) diagnosed with H. pylori infection and 230 healthy subjects were recruited in this study. The rs2072493, rs5744174, and rs5744168 polymorphisms within TLR5 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra-ARMS PCR genotyping techniques...
August 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28724760/uv-radiation-activates-toll-like-receptor-9-expression-in-primary-human-keratinocytes-an-event-inhibited-by-human-papillomavirus-type-38-e6-and-e7-oncoproteins
#19
Laura Pacini, Maria Grazia Ceraolo, Assunta Venuti, Giusi Melita, Uzma A Hasan, Rosita Accardi, Massimo Tommasino
Several lines of evidence indicate that cutaneous human papillomavirus (HPV) types belonging to the beta genus of the HPV phylogenetic tree synergise with UV radiation in the development of skin cancer. Accordingly, the E6 and E7 oncoproteins from some beta HPV types are able to deregulate pathways related to immune response and cellular transformation. Toll-like receptor 9 (TLR9), in addition to playing a role in innate immunity, has been shown to be involved in the cellular stress response. Using primary human keratinocytes (PHKs) as experimental models, we have shown that UV irradiation (and other cellular stresses) activates TLR9 expression...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28722236/the-membrane-type-estrogen-receptor-g-protein-coupled-estrogen-receptor-suppresses-lipopolysaccharide-induced-interleukin-6-via-inhibition-of-nuclear-factor-kappa-b-pathway-in-murine-macrophage-cells
#20
Mariko Okamoto, Takuto Suzuki, Yoichi Mizukami, Teruo Ikeda
The female sex hormone estrogen exerts anti-inflammatory effects. The G-protein-coupled estrogen receptor (GPER) has been recently identified as a novel membrane-type estrogen receptor that can mediate non-genomic estrogenic effects on many cell types. We previously demonstrated that GPER inhibits tumor necrosis factor alpha-induced expression of interleukin 6 (IL-6) through repression of nuclear factor-kappa B (NF-κB) promoter activity using human breast cancer cells. Although several reports have indicated that GPER suppresses Toll-like receptor-induced inflammatory cytokine expression in macrophages, the molecular mechanisms of the inhibition of cytokine production via GPER remain poorly understood...
July 18, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
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