• tlr9
• tlr7
• polymorphisms
• oral squamous cell carcinoma (oscc)
• prognosis
• survival
• oral cancer risk

• Humans
• Toll-Like Receptor 7/genetics
• Toll-Like Receptor 9/genetics
• Male
• Female
• Mouth Neoplasms/genetics
• Mouth Neoplasms/mortality
• Mouth Neoplasms/pathology
• Middle Aged
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/mortality
• Carcinoma, Squamous Cell/pathology
• Polymorphism, Single Nucleotide
• Aged
• Prognosis
• Genetic Predisposition to Disease
• Case-Control Studies
• Adult
• Genotype

• Toll-like receptor 9
• breast cancer
• systematic review

• R01 HL161386 NHLBI NIH HHS

• Digestive system tumors
• Nanomaterials
• Therapy
• Tumor immune microenvironment
• Tumor-associated macrophages

• cancer
• clinical treatment
• disease
• innate immunity
• toll‐like receptors

• Sichuan Province Science and Technology Support Program
• National Natural Science Foundation of China

• enteric viruses
• gut microbiota
• immune cells
• inflammatory bowel disease
• intestinal epithelial cells
• mucosal immunology
• pattern recognition receptors
• protein-coupled receptors

• Humans
• Inflammatory Bowel Diseases
• Gastrointestinal Microbiome
• Microbiota
• Immune System
• Intestines

• 2018YFA0508000 National Key R&D Program of China
• 82061148013 National Natural Science Foundation of China
• National Key R&D Program of China

• agonists
• antagonists
• chemotherapy
• human cancers
• immunotherapy
• therapeutic interventions
• toll-like receptors (TLRs)

• Humans
• Immunity, Innate
• Toll-Like Receptors/metabolism
• Neoplasms/drug therapy
• Signal Transduction
• Adaptive Immunity

• B cells
• erythrocytes
• immunomodulation
• neutrophils
• surface toll-like receptor 9

• Toll-Like Receptor 9
• Endosomes
• Erythrocytes
• Signal Transduction
• B-Lymphocytes

• National Natural Science Foundation of China

• EMT
• HIV
• NF-ĸB
• TLR
• colorectal cancer
• epigenetics
• inflammasome
• inflammation
• metastasis
• vimentin

• R01 CA252055 NCI NIH HHS
• 138139 National Research Foundation (NRF)
• 23108 South African Medical Research Foundation

• CRC
• TLR
• VDR
• colorectal cancer
• dysbiosis
• genetic variants
• microbial translocation
• polymorphisms

• N/A Gastrointestinal cancer study group
• No: 7387 / 19-02-2019 Hellenic Society of Medical Oncology (HeSMO)

• colorectal cancer
• gut micro-organisms
• immune cell
• intestinal inflammation
• intestinal microecology
• microbial-associated molecular patterns
• pattern recognition receptors
• probiotics
• toll-like receptors

Toll like receptors (TLRs) are a group of transmembrane receptors belonging to the class of pattern recognition receptors (PRR), which are involved in recognition of pathogen associated molecular patterns (PAMPs), inducing immune response. During the past decade, a number of preclinical and clinical breakthroughs in the field of TLR agonists has immerged in cancer research and some of these agents have performed exceptionally well in clinical trials. Based on evidence from scientific studies, we draw attention to several microbial based TLR agonists and discuss their relevance in various cancer and explore various microbial based TLR agonists for developing effective immunotherapeutic strategies against cancer.

Toll-like receptors (TLRs) are typical transmembrane proteins, which are essential pattern recognition receptors in mediating the effects of innate immunity. TLRs recognize structurally conserved molecules derived from microbes and damage-associated molecular pattern molecules that play an important role in inflammation. Since the first discovery of the Toll receptor by the team of J. Hoffmann in 1996, in Drosophila melanogaster, numerous TLRs have been identified across a wide range of invertebrate and vertebrate species. TLR stimulation leads to NF-κB activation and the subsequent production of pro-inflammatory cytokines and chemokines, growth factors and anti-apoptotic proteins. The expression of TLRs has also been observed in many tumors, and their stimulation results in tumor progression or regression, depending on the TLR and tumor type. The anti-tumoral effects can result from the activation of anti-tumoral immune responses and/or the direct induction of tumor cell death. The pro-tumoral effects may be due to inducing tumor cell survival and proliferation or by acting on suppressive or inflammatory immune cells in the tumor microenvironment. The aim of this review is to draw attention to the effects of TLR stimulation in cancer, the activation of various TLRs by microbes in different types of tumors, and, finally, the role of TLRs in anti-cancer immunity and tumor rejection.

• cancer
• immunotherapy
• innate receptors
• microbial based therapy
• toll like receptors

• Colorectal liver metastasis
• Gut microbiota
• Immune system
• Liver cancer
• Liver cancer treatment
• Primary liver cancer

• Carcinogenesis
• Dysbiosis
• Hepatocellular carcinoma
• Microbiota

• drug development
• innate immunity
• structural biology

• Animals
• Apoptosis/genetics
• Cellular Senescence/genetics
• DEAD Box Protein 58/genetics
• Host-Pathogen Interactions/genetics
• Humans
• Immunity, Innate/genetics
• Inflammation/genetics
• Inflammation/pathology
• Lectins, C-Type/genetics
• NLR Proteins/genetics
• Receptors, Immunologic/genetics
• Receptors, Pattern Recognition/genetics
• Toll-Like Receptors/genetics

• National Natural Science Foundation of China (National Science Foundation of China)

To investigate the association of human papillomavirus (HPV) status with p16, p53, and TLR9 expression in head and neck squamous cell carcinoma (HNSCC) and to evaluate these proteins as potential surrogate prognostic markers.

Expression of p16, p53, and TLR9 was assessed by immunohistochemistry, and HPV status was analyzed by in situ hybridization in 85 tumors of patients with HNSCC. Chi-square test was performed to evaluate the correlations of HPV infection with p16, p53, and TLR9 expression. Kaplan–Meier method and Cox regression analyses were applied to evaluate the associations between the expression levels of these proteins and patient outcomes.

Overall, 24 of the 85 HNSCC specimens were associated with HPV infection. High expression of p16, p53, and TLR9 in tumor cells was observed in 31.76%, 61.18%, and 49.41% of the specimens, respectively. p16 showed a higher diagnostic odds ratio for the prediction of HPV DNA positivity than p53 and TLR9. Improved 5-year overall and disease-free survival correlated with HPV positivity and high p16, low p53, and low TLR9 expression. Associations with improved outcomes were also observed for marker combinations high p16/low p53 and high p16/low p53/low TLR9. In a multivariate analysis, the high p16/low p53 signature showed the lowest hazard ratio regarding death.

The expression of p16, p53, and TLR9 in HNSCC is associated with HPV status. High p53 and TLR9 expression may be related to poor outcomes. The two-marker signature high p16/low p53 in tumor cells is a reliable tool for patient survival prognostication in HNSCC.

• TLR9
• head and neck squamous cell carcinoma
• human papillomavirus
• p16
• p53
• prognosis

Abnormal activation of Toll-like receptor (TLRs) signaling can result in colon cancer development. The aim of this study was to investigate the expression of important TLRs in different histological types of colorectal polyps and evaluate their relationship with intestinal microbiota. The expression levels of TLR2, 3, 4, and 5 were analyzed in intestinal biopsy specimens of 21 hyperplastic polyp (HP), 16 sessile serrated adenoma (SSA), 29 tubular adenoma (TA), 21 villous/tubulovillous (VP/TVP) cases, and 31 normal controls. In addition, selected gut bacteria including Streptococcus bovis, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. were quantified in fecal samples using absolute qRT PCR, and, finally, the association between TLRs and these gut microbiota- was evaluated by Spearman’s correlation coefficient. Higher expression of TLR2 and TLR4 in VP/TVP and TA, and lower expression levels of TLR3 and TLR5 in all type of polyps were observed. The differences in TLR expression patterns was not only dependent on the histology, location, size, and dysplasia grade of polyps but also related to the intestinal microbiota patterns. TLR2 and TLR4 expression was directly associated with the F. nucleatum, E. faecalis, S. bovis, Porphyromonas, and inversely to Bifidobacterium, Lactobacillus, and Roseburia quantity. Furthermore, TLR3 and TLR5 expression was directly associated with Bifidobacterium, Roseburia, and Lactobacillus quantity. Our results suggest a possible critical role of TLRs during colorectal polyp progression. An abnormal regulation of TLRs in relation to gut microbial quantity may contribute to carcinogenesis.

• Toll-like receptors
• colorectal polyps
• gut bacteria
• pattern recognition receptors

• Adenoma/genetics
• Adenoma/pathology
• Biodiversity
• Case-Control Studies
• Colonic Polyps/genetics
• Colonic Polyps/metabolism
• Colonic Polyps/microbiology
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Female
• Gastrointestinal Microbiome
• Gene Expression Regulation, Neoplastic
• Humans
• Hyperplasia/metabolism
• Male
• Middle Aged
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Toll-Like Receptors/genetics
• Toll-Like Receptors/metabolism

Primary liver cancer is one of the leading causes of cancer death worldwide. Surgical and non-surgical treatments are optional for liver cancer therapy based on the cancer stage. Accumulating studies show that the gut–liver axis influences the progression of liver diseases, including liver inflammation, fibrosis, cirrhosis, and cancer. However, the role of gut microbiota and their derived components and metabolites in liver cancer remains to be further clarified. In this review, we discuss the roles of gut microbiota and specific bacterial species in HCC and the strategies to modulate gut microbiota to improve antitumor therapy. Given the limitation of current treatments, gut microbiota-mediated therapy is a potential option for HCC treatment, including fiber diet and vegetable diet, antimicrobials, probiotics, and pharmaceutical inhibitors. Also, gut microbiota can be used as a marker for early diagnosis of HCC. HCC occurs dependent on various environmental and genetic factors, including diet and sex. Furthermore, gut microbiota impacts the immunotherapy of HCC treatment. Therefore, a better understanding of the role of the gut–liver axis in liver cancer is critically important to improve therapeutic efficacy.

• clinical trials
• gut microbiota
• liver cancer
• sex
• treatments

Chronic colorectal inflammation has been associated with colorectal cancer (CRC); however, its exact molecular mechanisms remain unclear. The present study aimed to investigate the effect of Toll-like receptor 9 (TLR9) on the development of colitis-associated CRC (CAC) through its regulation of the NF-κB signaling pathway. By using a CAC mouse model and immunohistochemistry, the present study discovered that the protein expression levels of TLR9 were gradually upregulated during the development of CRC. In addition, the expression levels of TLR9 were revealed to be positively correlated with NF-κB and Ki67 expression levels. In vitro, inhibiting TLR9 expression levels using chloroquine decreased the cell viability, proliferation and migration of the CRC cell line HT29, and further experiments indicated that this may occur through downregulating the expression levels of NF-κB, proliferating cell nuclear antigen and Bcl-xl. In conclusion, the findings of the present study suggested that TLR9 may serve an important role in the development of CAC by regulating NF-κB signaling.

• AOM
• DSS
• NF-κB
• TLR9
• colitis-associated CRC

Toll-like receptor 9 (TLR9) is a cellular DNA receptor of the innate immune system which plays a pivotal role in inflammatory response. Recently, changing expression levels of TLR9 has been observed in a wide range of cancer cells; however, there is little information about colorectal polyps. Herein, we assessed the mRNA expression of TLR9 in different colorectal polyp types compared to normal group in order to investigate its expression level during CRC initiation. Fifty-four biopsy samples from colorectal polyp patients and from 20 healthy subjects were collected. The mucosal mRNA expression level of TLR9 gene was identified by real time PCR. Fold change of gene expression was evaluated by 2^-ΔΔct method. There was a significant relationship between the lower expression of TLR9 gene in the polyp cases compared to normal individuals (P value = 0.0005), Also, decreased TLR9 mRNA expression was obtained in adenomas in contrast to hyperplastic and normal groups (P value = 0.0008). Based on the current results, we hypothesized that aberrant surface expression of TLR9 on tumor cells may promote the growth and invasion of colorectal polyps. Further, TLR9 modulation may have an important impact on the development of novel therapeutic strategies.

• Colorectal Polyp, mRNA expression
• TLR9