Toll like receptor 3 and cancer

Programmed cell death or apoptosis is a critically important mechanism of tissue remodeling and regulates conditions such as cancer, neurodegeneration or stroke. The aim of this research article was to assess the caged Z-DEVD-aminoluciferin substrate for in vivo monitoring of apoptosis after ischemic stroke in TLR2-deficient mice and their TLR2-expressing counterparts. Postischemic inflammation is a significant contributor to ischemic injury development and apoptosis, and it is modified by the TLR2 receptor...

Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) remains a deadly cancer worldwide with a need for new therapeutic approaches. A dysregulation in the equilibrium between pro- and anti-inflammatory responses with a predominant immunosuppressive inflammatory reaction in advanced stage tumors seem to contribute to tumor growth and metastasis. The current therapies do not include strategies against pro-tumorigenic inflammation in cancer patients. We have shown that the upregulated cell surface expression of Toll-like Receptor (TLR) 2 and of TLR9 inside PDAC cells maintain chronic inflammatory responses, support chemotherapeutic resistance, and mediate tumor progression in human pancreatic cancer...

Methotrexate (MTX), a chemotherapeutic antimetabolite, has been linked to cognitive impairment in cancer patients. MTX-induced metabolic pathway disruption may result in decreased antioxidant activity and increased oxidative stress, influencing hippocampal neurogenesis and microglial activation. Nuclear factor-kappa B (NF-κB), an oxidative stress byproduct, has been linked to MTX toxicity via the activation of NLRP3 inflammasome signaling. Macrophage activation and polarization plays an important role in tissue injury...

CONTEXT: The covalent acetylation and deacetylation of histone proteins by the histone deacetylase (HDAC) enzymes can be considered a novel therapeutic target in prostate cancer (PCa) cells. Sodium butyrate (NaBu) is a HDAC inhibitor (HDACi) which is a promising potential anticancer drug. Toll-like receptor 4 (TLR4) expression is increased in PCa cells and HDACi alter TLR-inducible gene expressions. AIMS: We aimed to evaluate the effects of NaBu on TLR4 mediating signaling pathways in two different PCa cells (DU-145 and LNCaP) for the first time...

MyD88 plays a central role in breast cancer, exerting a multitude of effects that carry substantial implications. Elevated MyD88 expression is closely associated with aggressive tumor characteristics, suggesting its potential as a valuable prognostic marker and therapeutic target. MyD88 exerts influence over several critical aspects of breast cancer, including metastasis, recurrence, drug resistance, and the regulation of cancer stem cell properties. Furthermore, MyD88 modulates the release of inflammatory and chemotactic factors, thereby shaping the tumor's immune microenvironment...

BACKGROUND: Type 2 diabetes is associated with higher risk of several cancer types. However, the biological intermediates driving this relationship are not fully understood. As novel interventions for treating and managing type 2 diabetes become increasingly available, whether they also disrupt the pathways leading to increased cancer risk is currently unknown. We investigated the effect of a type 2 diabetes intervention, in the form of intentional weight loss, on circulating proteins associated with cancer risk to gain insight into potential mechanisms linking type 2 diabetes and adiposity with cancer development...

The development and progression of breast cancer (BC) depend heavily on the tumor microenvironment (TME), especially tumor infiltration leukocytes (TILs). TME-based classifications in BC remain largely unknown and need to be clarified. Using the bioinformatic analysis, we attempted to construct a prognostic nomogram based on clinical features and TME-related differentially expressed genes (DEGs). We also tried to investigate the association between the prognostic nomogram and clinical characteristics, TILs, possible signaling pathways, and response to immunotherapy in BC patients...

Repolarizing the tumor-associated macrophages (TAMs) towards the antitumoral M1-like phenotype has been a promising approach for cancer immunotherapy. However, the anti-cancer immune response is severely limited mainly by the repolarized M1-like macrophages belatedly returning to the M2-like phenotype (i.e., negative feedback). Inspired by nitric oxide (NO) effectively preventing repolarization of inflammatory macrophages in inflammatory diseases, herein, we develop an arginine assembly, as NO nano-donor for NO generation to prevent the negative feedback of the macrophage repolarization...

Peptide-based vaccines have been widely investigated in cancer immunotherapy. Despite their high specificity, safety, and low production cost, these vaccines have shown limited success in clinical studies, owing to their poor immunogenicity. Extensive efforts have been devoted to increasing the immunogenicity of peptide vaccines by mixing peptides with adjuvants and/or promoting their delivery to tumor-draining lymph nodes (TdLNs) for better antigen presentation by and maturation of dendritic cells. Among these efforts, the exploration of various nanoparticles has been at the forefront of the rational design and construction of peptide-based vaccines...

Radiation therapy is frequently used to treat cancers including soft tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to radiation therapy (RT) in transplanted tumors, but the mechanism(s) remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft tissue sarcomas with high tumor mutation burden. Treatment with a single fraction of 20 Gy RT and two doses of CpG significantly enhanced tumor response, which was abrogated by genetic or immunodepletion of CD8+ T cells...

BACKGROUND: Toll-like receptors (TLRs) are a family of transmembrane receptors that play key roles in identifying invading pathogens and activating innate immunity. TLR1 has been reported to be associated with the risk of gastric cancer (GC) but that was based on only a simple statistical analysis. METHODS: We genotyped the TLR1 in 526 GC patients to investigate the association between the variation and gastric cancer survival by the multiplex polymerase chain reaction and sequencing method...

As a crucial protumorigenic long noncoding RNA, colorectal tumor differential expression (CRNDE) has been confirmed to facilitate the progression of various cancers. However, its role in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC) is still unclear. Here we determined that CRNDE was upregulated in HCC samples and that CRNDE-positive cells were predominantly enriched in malignant tumor cells. In vivo functional assays revealed that CRNDE-induced tumor cells supported HCC progression, recruited abundant granulocyte myeloid-derived suppressor cells (G-MDSCs) and restricted the infiltration of T cells...

This study assessed the safety and efficacy of OncoTherad® (MRB-CFI-1) nanoimmunotherapy for non-muscle invasive bladder cancer (NMIBC) patients unresponsive to Bacillus Calmette-Guérin (BCG) and explored its mechanisms of action in a bladder cancer microenvironment. A single-arm phase I/II study was conducted with 44 patients with NMIBC who were unresponsive to BCG treatment. Primary outcomes were pathological complete response (pCR) and relapse-free survival (RFS). Secondary outcomes comprised response duration and therapy safety...

PURPOSE: To investigate the anti-tumor effect of Robinin (Toll-like receptor 2 inhibitor) in pancreatic cancer cells via regulating tumor microenvironment. METHODS: The effects of Robinin on cell proliferation or migration in Mia-PACA2 and PANC-1 were determined, using CCK8 or wound healing assay, respectively. The typical markers of EMT (αSMA and snail) and the inflammation markers (IL-6 and TNF-α) were all detected by western blot. CU-T12-9 (TLR2 agonist) was used to rescue Robinin's effect...

Protease activated receptors (PARs) are cleaved by coagulation proteases and thereby connect hemostasis with innate immune responses. Signaling of the tissue factor (TF) complex with FVIIa via PAR2 stimulates extracellular signal-regulated kinase (ERK) activation and cancer cell migration, but functions of cell autonomous TF-FVIIa signaling in immune cells are unknown. Here we show that myeloid cell expression of FVII but not of FX is crucial for inflammatory cell recruitment to the alveolar space after challenge with the double stranded viral RNA mimic Poly(I:C)...

β-Glucans are valuable functional polysaccharides distributed in nature, especially in the cell walls of fungi, yeasts, bacteria, and cereals. The unique features of β-glucans, such as water solubility, viscosity, molecular weight, and so on, have rendered them to be broadly applied in various food systems as well as in medicine to improve human health. Moreover, inhibition of cancer development could be achieved by an increase in immune system activity via β-glucans. β-glucans, which are part of a class of naturally occurring substances known as biological response modifiers (BRMs), have also shown evidence of being anti-tumorogenic, anti-cytotoxic, and anti-mutagenic...

INTRODUCTION: Nonhuman adenoviral (AdV) gene delivery platforms have significant value due to their ability to elude preexisting AdV vector immunity in most individuals. Previously, we have demonstrated that intranasal (IN) immunization of mice with BAd-H5HA, a bovine AdV type 3 (BAdV3) vector expressing H5N1 influenza virus hemagglutinin (HA), resulted in enhanced humoral and cell-mediated immune responses. The BAd-H5HA IN immunization resulted in complete protection following the challenge with an antigenically distinct H5N1 virus compared to the mouse group similarly immunized with HAd-H5HA, a human AdV type 5 (HAdV5) vector expressing HA...

The percentage of head and neck cancer (HNC) positive for human papillomavirus (HPV) is unknown in most parts of India. How toll-like receptors (TLRs) affect the adaptive immune response in HNC is also mainly unknown. We here assessed the expressions of HPV DNA, p16, inflammation, and TLRs in oral squamous cell carcinoma (OC) and oropharyngeal squamous cell carcinoma (OPC). Patients with OC ( n  = 31) and OPC ( n  = 41), diagnosed during 2017-2018 at the Malabar Cancer Centre (tertiary cancer center), Kerala, India, were included in the study...

Toll-like receptor 3 (TLR3) is a prominent member of the Toll-like receptor (TLR) family and has the ability to recognize and bind intracellular double-stranded RNA (dsRNA). Once triggered by a viral infection or other pathological condition, TLR3 activates immune cells and induces the production of interferons and other immune response molecules. Additionally, TLR3 is considered an important immune modulator, as it can regulate cell apoptosis and promote anticancer immunity. The investigation and application of TLR3 agonists in digestive system tumors have attracted widespread attention and are regarded as a promising cancer treatment strategy with potential clinical applications...

Lung cancer and asthma are both global health problems with significant economic consequences. Recent studies have demonstrated that asthma may be a risk factor for lung cancer. The present study aimed to explore the pathogenesis between these two diseases through a comprehensive analysis. Differentially expressed genes (DEGs) screened in the asthma-related GSE165934 dataset were analyzed to find relevant inflammatory pathways. Overlapping genes regulated by inflammatory pathways and lung cancer-DEGs from The Cancer Genome Atlas (TCGA) were obtained and subjected to survival and gene-wide mutation analyses, and nomogram construction to determine the hub gene...