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Toll like receptors and cancer

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https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#1
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#2
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205610/cr-laao-an-l-amino-acid-oxidase-from-calloselasma-rhodostoma-venom-as-a-potential-tool-for-developing-novel-immunotherapeutic-strategies-against-cancer
#3
Tássia R Costa, Danilo L Menaldo, Karina F Zoccal, Sandra M Burin, Alexandre F Aissa, Fabíola A de Castro, Lúcia H Faccioli, Lusânia M Greggi Antunes, Suely V Sampaio
L-amino acid oxidases from snake venoms have been described to possess various biological functions. In this study, we investigated the inflammatory responses induced in vivo and in vitro by CR-LAAO, an L-amino acid oxidase isolated from Calloselasma rhodostoma venom, and its antitumor potential. CR-LAAO induced acute inflammatory responses in vivo, with recruitment of neutrophils and release of IL-6, IL-1β, LTB4 and PGE2. In vitro, IL-6 and IL-1β production by peritoneal macrophages stimulated with CR-LAAO was dependent of the activation of the Toll-like receptors TLR2 and TLR4...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#4
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28194462/designing-an-efficient-multi-epitope-oral-vaccine-against-helicobacter-pylori-using-immunoinformatics-and-structural-vaccinology-approaches
#5
Navid Nezafat, Mahboobeh Eslami, Manica Negahdaripour, Mohammad Reza Rahbar, Younes Ghasemi
Helicobacter pylori is the cunning bacterium that can live in the stomachs of many people without any symptoms, but gradually can lead to gastric cancer. Due to various obstacles, which are related to anti-H. pylori antibiotic therapy, recently developing an anti-H. pylori vaccine has attracted more attention. In this study, different immunoinformatics and computational vaccinology approaches were employed to design an efficient multi-epitope oral vaccine against H. pylori. Our multi-epitope vaccine is composed of heat labile enterotoxin IIc B (LT-IIc) that is used as a mucosal adjuvant to enhance vaccine immunogenicity for oral immunization, cartilage oligomeric matrix protein (COMP) to increase vaccine stability in acidic pH of gut, one experimentally protective antigen, OipA, and two hypothetical protective antigens, HP0487 and HP0906, and "CTGKSC" peptide motif that target epithelial microfold cells (M cells) to enhance vaccine uptake from the gut barrier...
February 14, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28191612/high-toll-like-receptor-tlr-9-expression-is-associated-with-better-prognosis-in-surgically-treated-pancreatic-cancer-patients
#6
Joni Leppänen, Olli Helminen, Heikki Huhta, Joonas H Kauppila, Joel Isohookana, Kirsi-Maria Haapasaari, Petri Lehenkari, Juha Saarnio, Tuomo J Karttunen
Pancreatic cancer remains one of the deadliest malignancies in the world. Inflammatory response and tumor environment are thought to play a major role in its pathogenesis. Knowledge on TLR expression and impact on patient survival in pancreatic cancer is limited. The study's aim was to clarify the role of different TLRs in pancreatic cancer. TLR2, TLR4, and TLR9 expression was investigated in 65 surgically resected pancreatic ductal adenocarcinoma specimens by immunohistochemistry. The association between TLR expression, clinical parameters, and local inflammatory response to the tumor was assessed using chi-square test...
February 12, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28191009/defective-il-23-il-17-axis-protects-p47phox-mice-from-colon-cancer
#7
Cornelia Richter, Martina Herrero San Juan, Benno Weigmann, Dominik Bergis, Katrin Dauber, Michael H Muders, Gustavo B Baretton, Josef Martin Pfeilschifter, Halvard Bonig, Sebastian Brenner, Heinfried H Radeke
In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28186087/baculovirus-directly-activates-murine-nk-cells-via-tlr9
#8
T Moriyama, T Suzuki, M O Chang, M Kitajima, H Takaku
The importance of natural killer (NK) cells in innate immune responses against tumors or viral infections enhances the appeal of NK cell-based immunotherapeutic approaches. We have recently reported that baculovirus (BV)-infected dendritic cells (DCs; BV-DCs) induce antitumor immunity against established tumors in mice. These antitumor effects were CD8(+) T-cell and NK cell dependent; however, they were found to be CD4(+) T-cell independent. In this study, we investigated the involvement of Toll-like receptor 9 (TLR9) in the process of BV recognition by NK cells...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28179508/two-step-enhanced-cancer-immunotherapy-with-engineered-salmonella-typhimurium-secreting-heterologous-flagellin
#9
Jin Hai Zheng, Vu H Nguyen, Sheng-Nan Jiang, Seung-Hwan Park, Wenzhi Tan, Seol Hee Hong, Myung Geun Shin, Ik-Joo Chung, Yeongjin Hong, Hee-Seung Bom, Hyon E Choy, Shee Eun Lee, Joon Haeng Rhee, Jung-Joon Min
We report a method of cancer immunotherapy using an attenuated Salmonella typhimurium strain engineered to secrete Vibrio vulnificus flagellin B (FlaB) in tumor tissues. Engineered FlaB-secreting bacteria effectively suppressed tumor growth and metastasis in mouse models and prolonged survival. By using Toll-like receptor 5 (TLR5)-negative colon cancer cell lines, we provided evidence that the FlaB-mediated tumor suppression upon bacterial colonization is associated with TLR5-mediated host reactions in the tumor microenvironment...
February 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28174027/forkhead-box-p3-regulatory-t-cells-and-toll-like-receptor-2-co-expression-in-oral-squamous-cell-carcinoma
#10
H M Hussaini, V P B Parachuru, G J Seymour, A M Rich
BACKGROUND: The function of forkhead box-P3 (FoxP3) regulatory T cells (Treg) and toll-like receptor (TLR)2 protein in the oral cancer microenvironment is not fully understood, but evidence from other malignancies suggests it is likely they are involved with tumour development and progression. The aim of this study was to investigate the distribution of FoxP3(+)cells, TLR2(+) cells and double-labelled FoxP3(+)TLR2(+) immune cells in oral squamous cell carcinoma (OSCC), using immunohistochemistry (IHC) and immunofluorescence (IF)...
February 4, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28153581/delivery-of-tlr7-agonist-to-monocytes-and-dendritic-cells-by-dcir-targeted-liposomes-induces-robust-production-of-anti-cancer-cytokines
#11
Thomas C B Klauber, Janne M Laursen, Daniel Zucker, Susanne Brix, Simon S Jensen, Thomas L Andresen
: Tumor immune escape is today recognized as an important cancer hallmark and is therefore a major focus area in cancer therapy. Monocytes and dendritic cells (DCs), which are central to creating a robust anti-tumor immune response and establishing an anti-tumorigenic microenvironment, are directly targeted by the tumor escape mechanisms to develop immunosuppressive phenotypes. Providing activated monocytes and DCs to the tumor tissue is therefore an attractive way to break the tumor-derived immune suppression and reinstate cancer immune surveillance...
January 30, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28151089/role-of-tlr9-in-oncogenic-virus-produced-cancer
#12
Cecilia Martínez-Campos, Ana I Burguete-García, Vicente Madrid-Marina
Nucleic acid recognition by toll-like receptor 9 (TLR9) initiates signaling pathways that regulate the production of proinflammatory cytokines or type I interferons, as well as many other molecules required to initialize the immune response. The use of synthetic oligodeoxynucleotides (ODNs) has been crucial to emulate the recognition of DNA sequences by TLR9. Furthermore, ODN administration to mice has shown to confer protection against a wide range of viral, bacterial, and parasitic pathogens. In contrast, oncogenic DNA viruses like hepatitis B virus, Epstein-Barr virus, and human papilloma virus inhibit TLR9 expression, thus contributing to the establishment of chronic viral infections...
February 2, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28144136/cpg-oligodeoxynucleotide-nanomedicines-for-the-prophylaxis-or-treatment-of-cancers-infectious-diseases-and-allergies
#13
REVIEW
Nobutaka Hanagata
Unmethylated cytosine-guanine dinucleotide-containing oligodeoxynucleotides (CpG ODNs), which are synthetic agonists of Toll-like receptor 9 (TLR9), activate humoral and cellular immunity and are being developed as vaccine adjuvants to prevent or treat cancers, infectious diseases, and allergies. Free CpG ODNs have been used in many clinical trials implemented to verify their effects. However, recent research has reported that self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes demonstrate higher adjuvant effects than free CpG ODNs, owing to their improved uptake efficiency into cells expressing TLR9...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28138030/the-tlr3-agonist-inhibit-drug-efflux-and-sequentially-consolidates-low-dose-cisplatin-based-chemoimmunotherapy-while-reducing-side-effects
#14
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, XiaoFeng Huang, Jianjian Ji, Qingang Hu, Hui Wang, Yanhong Ni, Yayi Hou
The traditional maximum dose density chemotherapy renders the tumor patients not only the tumor remission but the chemotherapy resistance and more adverse side effects. According to the widely positive expression of Toll-like receptor (TLR)-3 in oral squamous cell carcinoma (OSCC) patients (n=166), we here provided an alternative strategy involved the orderly treatment of TLR3 agonist polyinosine-polycytidylic acid (PIC) and low-dose cisplatin. The optimal dose of cisplatin, the novel role of PIC and the side effects of the combined chemotherapy were determined in vitro and in distinct human tumor models in vivo...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28137827/s100a9-induces-differentiation-of-acute-myeloid-leukemia-cells-through-tlr4
#15
Malika Laouedj, Mélanie R Tardif, Laurine Gil, Marie-Astrid Raquil, Asmaa Lachaab, Martin Pelletier, Philippe A Tessier, Frédéric Barabé
S100A8 and S100A9 are calcium-binding proteins predominantly expressed by neutrophils and monocytes, and play key roles in both normal and pathological inflammation. Recently, both proteins were found to promote tumor progression through the establishment of pre-metastatic niches and to inhibit antitumor immune responses. Although S100A8 and S100A9 have been studied in solid cancers, their functions in hematological malignancies remain poorly understood. However, S100A8 and S100A9 are highly expressed in acute myeloid leukemia (AML), and S100A8 expression has been linked to a poor prognosis in AML...
January 30, 2017: Blood
https://www.readbyqxmd.com/read/28126350/peptostreptococcus-anaerobius-induces-intracellular-cholesterol-biosynthesis-in-colon-cells-to-induce-proliferation-and-causes-dysplasia-in-mice
#16
Ho Tsoi, Eagle Sh Chu, Xiang Zhang, Jianqiu Sheng, Daniel Nakatsu, Siew C Ng, Anthony Wh Chan, Francis Kl Chan, Joseph Jy Sung, Jun Yu
BACKGROUND & AIMS: Stool samples from patients with colorectal cancer (CRC) have a higher abundance of Peptostreptococcus anaerobius than stool from individuals without CRC, based on metagenome sequencing. We investigated whether P anaerobius contributes to colon tumor formation in mice and its possible mechanisms of carcinogenesis. METHODS: We performed quantitative PCR analyses to measure P anaerobius in 112 stool samples and 255 colon biopsies from patients with CRC or advanced adenoma and from healthy individuals (controls) undergoing colonoscopy examination at hospitals in Hong Kong and Beijing...
January 23, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28114604/topical-imiquimod-plus-nab-paclitaxel-for-breast-cancer-cutaneous-metastases-a-phase-2-clinical-trial
#17
Lupe G Salazar, Hailing Lu, Jessica L Reichow, Jennifer S Childs, Andrew L Coveler, Doreen M Higgins, James Waisman, Kimberly H Allison, Yushe Dang, Mary L Disis
Importance: Salvage chemotherapy for recurrent chest wall lesions in breast cancer results in response rates of 20% to 30%. Preclinical studies showed significant disease regression could be induced in murine chest wall mammary cancers with a topical toll-like receptor (TLR)-7 agonist, imiquimod. Objective: To evaluate the safety and objective response rate (ORR) of imiquimod in combination with systemic albumin bound paclitaxel in treatment-refractory breast cancer of the chest wall...
January 19, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28114253/intratumoral-approaches-for-the-treatment-of-melanoma
#18
Praveen K Bommareddy, Ann W Silk, Howard L Kaufman
There have been significant advances in the immunotherapy of melanoma over the last decade. The tumor microenvironment is now known to promote an immune-suppressive milieu that can block effective immune-mediated tumor rejection. Several novel strategies designed to overcome local immunosuppression hold promise for treatment of melanoma and other cancers. These approaches include oncolytic viruses, plasmid DNA delivery, Toll-like receptor agonists, inflammatory dyes, cytokines, checkpoint inhibitors, immunomodulatory agents, and host and pathogenic cell-based vectors...
January 2017: Cancer Journal
https://www.readbyqxmd.com/read/28110170/tailoring-polymeric-hybrid-micelles-with-lymph-node-targeting-ability-to-improve-the-potency-of-cancer-vaccines
#19
Qin Zeng, Hanmei Li, Hao Jiang, Jiao Yu, Ying Wang, Huan Ke, Tao Gong, Zhirong Zhang, Xun Sun
It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines and particles sized between 10 and 100 nm with a neutral or negative surface charge are preferred for lymphatic transfer after subcutaneous or intradermal injection. However their limited uptake by antigen presenting cells (APCs) and inadequate retention within LNs undoubtedly restrains their strength on activating T cell immunity. Here, we address this issue by tailoring the physicochemical properties of polymeric hybrid micelles (HMs), which are self-assembled from two amphiphilic diblock copolymers, poly-(ethylene glycol) phosphorethanolamine (PEG-PE) and polyethylenimine-stearic acid conjugate (PSA) via hydrophobic and electrostatic interactions...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28110064/activation-of-dendritic-cells-by-low-molecular-weight-oyster-polysaccharides
#20
Ming Zhong, Cheng Zhong, Tingting Wang, Pei Hu, Guanghui Wang, Rujing Ren, Jing Zhang, Huijei Gao, Wen Cui, Wenjuan Duan, Jiantu Che
Dendritic cells play a primary role in antigen presentation to CD4(+) T cells, which initiate acquired immune responses. Therefore, determining positive modulators of dendritic cell activation to improve therapeutic approaches for cancer treatment might be useful. We here investigated the effects of low molecular weight oyster polysaccharides (LMW-OPS) on bone marrow-derived dendritic cells (BMDCs) obtained from mice. LMW-OPS increased the surface expression of major histocompatibility complex class II (MHC-II), CD40 and CD86 in BMDCs and induced the secretion of tumour necrosis factor (TNF)-α and interleukin (IL)-12, which were significantly decreased in the BMDCs derived from MyD88(-/-) mice but not from the lipopolysaccharide-resistant C3H/HeJ mice...
January 18, 2017: International Immunopharmacology
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