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TLR lung cancer

Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
C Jungnickel, L H Schmidt, L Bittigkoffer, L Wolf, A Wolf, F Ritzmann, A Kamyschnikow, C Herr, M D Menger, T Spieker, R Wiewrodt, R Bals, C Beisswenger
Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for lung cancer and an aberrant microbiota of the lung. Microbial colonization contributes to chronic neutrophilic inflammation in COPD. Nontypeable Haemophilus influenzae (NTHi) is frequently found in lungs of stable COPD patients and is the major pathogen triggering exacerbations. The epithelial cytokine interleukin-17C (IL-17C) promotes the recruitment of neutrophils into inflamed tissues. The purpose of this study was to investigate the function of IL-17C in the pulmonary tumor microenvironment...
March 27, 2017: Oncogene
Katja Hattar, Christian P Reinert, Ulf Sibelius, Mira Y Gökyildirim, Florentine S B Subtil, Jochen Wilhelm, Bastian Eul, Gabriele Dahlem, Friedrich Grimminger, Werner Seeger, Ulrich Grandel
Pulmonary infections are frequent complications in lung cancer and may worsen its outcome and survival. Inflammatory mediators are suspected to promote tumor growth in non-small-cell lung cancer (NSCLC). Hence, bacterial pathogens may affect lung cancer growth by activation of inflammatory signalling. Against this background, we investigated the effect of purified lipoteichoic acids (LTA) of Staphylococcus aureus (S. aureus) on cellular proliferation and liberation of interleukin (IL)-8 in the NSCLC cell lines A549 and H226...
March 17, 2017: Cancer Immunology, Immunotherapy: CII
Christopher Jungnickel, Philipp A Schnabel, Rainer Bohle, Rainer Wiewrodt, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic obstructive pulmonary disease is a risk factor for lung cancer. COPD is characterized by chronic airway inflammation and lung infections. The airways of patients with COPD are frequently colonized with bacteria [eg, nontypeable Haemophilus influenzae (NTHi)] that cause pulmonary inflammation and exacerbations. Pulmonary adenocarcinomas are frequently associated with an activating mutation in the KRAS gene. We determined the function of Toll-like receptor (TLR) signaling on the progression of KRas-induced early adenomatous lesions in the lung...
March 6, 2017: American Journal of Pathology
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...
April 11, 2017: Oncotarget
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
Haitao Shen, Na Wu, Zhenning Liu, Hongyu Zhao, Min Zhao
AIMS: To evaluate the detoxifying effect of epigallocatechin-3-gallate (EGCG) on paraquat (PQ)-induced acute lung injury in mice, and to explore the action mechanisms. MAIN METHODS: Following administration of PQ, the mice received a low, a medium or a high dose of EGCG daily for three days. Histopathology of the lungs were examined by H&E staining. The levels of inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay...
February 1, 2017: Life Sciences
C P Belani, B C Chakraborty, R I Modi, B M Khamar
Background: Randomized controlled trial to evaluate synergy between taxane plus platinum chemotherapy and CADI-05, a Toll like receptor-2 agonist targeting desmocollin-3 as a first-line therapy in advanced non-small-cell lung cancer (NSCLC). Patients and methods: Patients with advanced NSCLC (stage IIIB or IV) were randomized to cisplatin-paclitaxel (chemotherapy group, N = 112) or cisplatin-paclitaxel plus CADI-05 (chemoimmunotherapy group, N = 109). CADI-05 was administered a week before chemotherapy and on days 8 and 15 of each cycle and every month subsequently for 12 months or disease progression...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Darlene A Monlish, Sima T Bhatt, Laura G Schuettpelz
Toll-like receptors (TLRs) are a family of pattern recognition receptors that shape the innate immune system by identifying pathogen-associated molecular patterns and host-derived damage-associated molecular patterns. TLRs are widely expressed on both immune cells and non-immune cells, including hematopoietic stem and progenitor cells, effector immune cell populations, and endothelial cells. In addition to their well-known role in the innate immune response to acute infection or injury, accumulating evidence supports a role for TLRs in the development of hematopoietic and other malignancies...
2016: Frontiers in Immunology
Anna Pomerenke, Simon R Lea, Sarah Herrick, Mark A Lindsay, Dave Singh
PURPOSE: Viruses are a common cause of exacerbations in chronic obstructive pulmonary disease (COPD). They activate toll-like receptors (TLRs) 3, 7, and 8, leading to a pro-inflammatory response. We have characterized the responses of TLR3 and TLR7/8 in lung tissue explants from COPD patients and control smokers. METHODS: We prepared lung whole tissue explants (WTEs) from patients undergoing surgery for confirmed or suspected lung cancer. In order to mimic the conditions of viral infection, we used poly(I:C) for TLR3 stimulation and R848 for TLR7/8 stimulation...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Priyanka Khare, Anjali Bose, Poonam Singh, Sandhya Singh, Saleem Javed, Swatantra Kumar Jain, Om Singh, Rahul Pal
Human chorionic gonadotropin (hCG), a hormone essential for pregnancy, is also ectopically expressed by a variety of cancers and is associated with poor prognosis; molecular mechanisms which may contribute to tumor progression remain ill-defined. Exogenous hCG enhanced the viability of human colorectal and lung cancer cells and promoted the growth of syngeneic tumors in mice. It induced the synthesis of VEGF, IL-8, matrix metalloprotease (MMP)-2 and MMP-9, and increased invasiveness in an MMP-dependent manner...
February 2017: Molecular Carcinogenesis
Xiaoxia Li, Shihua Wang, Rongjia Zhu, Hongling Li, Qin Han, Robert Chunhua Zhao
BACKGROUND: In tumor microenvironment, a continuous cross-talk between cancer cells and other cellular components is required to sustain tumor progression. Accumulating evidence suggests that exosomes, a novel way of cell communication, play an important role in such cross-talk. Exosomes could facilitate the direct intercellular transfer of proteins, lipids, and miRNA/mRNA/DNAs between cells. Since mesenchymal stem cells (MSCs) can be attracted to tumor sites and become an important component of the tumor microenvironment, there is an urgent need to reveal the effect of tumor exosomes on MSCs and to further explore the underlying molecular mechanisms...
April 18, 2016: Journal of Hematology & Oncology
Selvi Ramasamy, Borja Saez, Subhankar Mukhopadhyay, Daching Ding, Alwiya M Ahmed, Xi Chen, Ferdinando Pucci, Rae'e Yamin, Jianfeng Wang, Mikael J Pittet, Cassandra M Kelleher, David T Scadden, David A Sweetser
Tle1 (transducin-like enhancer of split 1) is a corepressor that interacts with a variety of DNA-binding transcription factors and has been implicated in many cellular functions; however, physiological studies are limited. Tle1-deficient (Tle1(Δ/Δ)) mice, although grossly normal at birth, exhibit skin defects, lung hypoplasia, severe runting, poor body condition, and early mortality. Tle1(Δ/Δ) mice display a chronic inflammatory phenotype with increased expression of inflammatory cytokines and chemokines in the skin, lung, and intestine and increased circulatory IL-6 and G-CSF, along with a hematopoietic shift toward granulocyte macrophage progenitor and myeloid cells...
February 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
Pramod Kumar Gupta, Devavrat Tripathi, Savita Kulkarni, M G R Rajan
Chronic infections of Mycobacterium tuberculosis (MTB) cause oxidative stress, TLR activation and production of inflammatory cytokines and thus can create an environment reinforcing tumorigenesis, progression and metastasis. Epidemiological studies have established a relation between lung cancer and tuberculosis but cellular mechanism is still poorly understood. In present study, we have shown for the first time that MTB infection in human monocytic cell line (THP-1) enhances invasion and induces EMT characteristics in lung adenocarcinoma cell line (A549) during co-culture...
February 2016: Cellular Immunology
Pini Matzner, Liat Sorski, Lee Shaashua, Ely Elbaz, Hagar Lavon, Rivka Melamed, Ella Rosenne, Neta Gotlieb, Amit Benbenishty, Steve G Reed, Shamgar Ben-Eliyahu
The use of TLR agonists as an anti-cancer treatment is gaining momentum given their capacity to activate various host cellular responses through the secretion of inflammatory cytokines and type-I interferons. It is now also recognized that the perioperative period is a window of opportunity for various interventions aiming at reducing the risk of cancer metastases-the major cause of cancer related death. However, immune-stimulatory approach has not been used perioperatively given several contraindications to surgery...
April 1, 2016: International Journal of Cancer. Journal International du Cancer
Hulyam Kurt, Cansu Ozbayer, Aysegul Bayramoglu, Hasan Veysi Gunes, İrfan Degirmenci, Kevser Setenay Oner, Muzaffer Metintas
Chronic inflammation triggers DNA damage and oncogenic mutations and causes tumor formation and tumor progression. One of the important components of the inflammatory response is Toll-like receptor (TLR) family. The objective of our study is to determine the relationship between rs4986790(+896A/G) and rs4986791(+1196C/T) gene polymorphisms and lung cancer risk. PCR-RFLP technique was carried out to identify the genotypes in 100 control individuals and 160 lung cancer patients. DNA extracted from peripheral blood samples were amplified and digested with NcoI and HinfI then visualized...
February 2016: Inflammation
Renata Ursu, Sophie Taillibert, Claire Banissi, Eric Vicaut, Olivier Bailon, Emilie Le Rhun, Jean-Sebastien Guillamo, Dimitri Psimaras, Annick Tibi, Adama Sacko, Athina Marantidou, Catherine Belin, Antoine F Carpentier
TLR-9 agonists are immunostimulating agents that have antitumor effects in animal models. A phase I trial was conducted to define the safety profile of subcutaneous injections, combined with intrathecally administration of CpG-28, a TRL 9 agonist, in patients with neoplastic meningitis (NM). Cohorts of 3-6 patients with NM were treated for 5 weeks with escalating doses of CpG-28. The primary endpoint was tolerance. Secondary endpoints were progression free survival (PFS) and overall survival (OS). Twenty-nine patients were treated with CpG-28...
September 2015: Cancer Science
Chiara Storti, Valentino Le Noci, Michele Sommariva, Elda Tagliabue, Andrea Balsari, Lucia Sfondrini
Intratumoral delivery of drugs, enabling increased local concentrations in the tumor microenvironment, might be superior to systemic administration in promoting antitumor activity and minimizing the systemic side effects of some drugs. Unfortunately, not all human cancers are amenable to drug injection into the tumor site. Lung cancers are candidate tumors for taking advantage of local delivery, being accessible via the endobronchial space by aerosol administration. Inhalation of aerosolized drugs is a promising option in the management of lung diseases and currently represents the standard treatment for asthma and chronic obstructive pulmonary disease...
2015: Current Cancer Drug Targets
Araceli García-Castro, Manuela Zonca, Douglas Florindo-Pinheiro, Carla E Carvalho-Pinto, Alex Cordero, Burgo Gutiérrez del Fernando, Aránzazu García-Grande, Santos Mañes, Michael Hahne, Eva González-Suárez, Lourdes Planelles
APRIL (a proliferation-inducing ligand) is a cytokine of the tumor necrosis factor family associated mainly with hematologic malignancies. APRIL is also overexpressed in breast carcinoma tissue lesions, although neither its role in breast tumorigenesis nor the underlying molecular mechanism is known. Here, we show that several breast cancer cell lines express APRIL and both its receptors, B cell maturation antigen (BCMA) and transmembrane activator and CAML-interactor (TACI), independently of luminal or basal tumor cell phenotype, and that the mitogen-activated protein kinases p38, ERK1/2, and JNK1/2 are activated in response to APRIL...
May 2015: Carcinogenesis
Barbara Behm, Pietro Di Fazio, Patrick Michl, Daniel Neureiter, Ralf Kemmerling, Eckhart Georg Hahn, Deike Strobel, Thomas Gress, Detlef Schuppan, Thaddaeus Till Wissniowski
INTRODUCTION: Radiofrequency ablation (RFA), a palliative therapeutic option for solid hepatic tumours, stimulates localised and systemic antitumour cytotoxic T cells. We studied how far addition of CpG B oligonucleotides, toll like receptor (TLR) 9 agonists, would increase the antitumoural T cell response of RFA in the highly aggressive VX2 hepatoma. METHODS: Rabbits were randomised to receive RFA, CpG B, their combination or no therapy. The antitumour efficacy of RFA alone or in combination with CpG B was further tested by rechallenging a separate group with intravenously injected VX2 tumour cells after 120 days...
January 2016: Gut
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