Toll‐like receptors: A pathway alluding to cancer control

Ayala-Cuellar, Ana Patricia; Cho, Jaejin; Choi, Kyung‐Chul

doi:10.1002/jcp.28879

Cited by 28 publications

(13 citation statements)

References 75 publications

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“…TLRs are mainly expressed in immune cells to recognize pathogen-associated molecular patterns or damage-associated molecular patterns (Kawasaki and Kawai, 2014). Recent studies also reveal the antitumor effects of TLRs (Ayala-Cuellar et al, 2019). Innate immune cells can secrete cytokines to kill cancer cells, or recruit adaptive immune cells through the activation of TLR signaling pathways (Olbert et al, 2015a;Dajon et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Toll-Like Receptor 4 as a Favorable Prognostic Marker in Bladder Cancer: A Multi-Omics Analysis

Xia

Sun

et al. 2021

Front. Cell Dev. Biol.

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BackgroundThe toll-like receptor 4 (TLR4) agonist, Bacille Calmette-Guérin, has exhibited gratifying effects in treating bladder cancer. The study aims to explore the expression pattern, prognostic value, and potential mechanism of TLR4 in bladder cancer.MethodsThe transcriptome file from the GSE13507 dataset in the Gene Expression Omnibus database and the promoter methylation file from the bladder cancer dataset in The Cancer Genome Atlas database were downloaded for analysis. The prognostic value of the TLRs was assessed by univariate Cox regression. Immunohistochemistry was applied to verify the expression of TLR4 in bladder cancer. The drug response is estimated through the R package “pRRophetic.” The CIBERSORT algorithm was carried out to estimate the infiltrating immune cells of samples. Gene Set Enrichment Analysis (GSEA) was performed to identify the pathways involved under varied TLR4 expression levels.ResultsTLR4 is decreased in tumor tissues compared with surrounding tumor tissues or normal tissue, which is also positively correlated to the overall survival rate (hazard ratio [HR] = 0.38) and cancer-specific survival rate (HR = 0.15) of patients with bladder cancer. Low expression of TLR4 is observed in tumors with malignant performance (high pathological grade, higher tumor stage, and progression). Patients with low TLR4 levels are more sensitive to gemcitabine rather than cisplatin. The promoter methylation level of TLR4 is positively associated with TLR4 expression (P < 0.001). The cg14629571 methylation site largely contributes to the overall methylation level. The CIBERSORT analysis shows that high TLR4 expression is associated with lower levels of plasma cells, M0 macrophages, and M1 macrophages. The GSEA results indicate that the TGF-β pathway and apoptosis are activated in high TLR4 bladder cancer, while G2M checkpoint and E2F targets pathways are enriched in low TLR4 bladder cancer.ConclusionThis research discusses the abnormal expression and prognostic value of TLR4 in bladder cancer. The TLR4 expression can effectively predict oncological outcomes and drug sensitivity of bladder cancer patients. TLR4 is also associated with infiltrating immune cell variation and cancer pathway dysregulation. The results provide a novel prognostic marker and potential drug targets for bladder cancer.

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Section: Introductionmentioning

confidence: 99%

Toll-Like Receptor 4 as a Favorable Prognostic Marker in Bladder Cancer: A Multi-Omics Analysis

Xia

Sun

et al. 2021

Front. Cell Dev. Biol.

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“…Anti-microbial treatment resulted in an increased intratumoral CD8:CD4 T cell ratio, promoting Th1 differentiation of CD4+ T cells and CD8+ T cell activation ( 16 ). Microorganisms in PDAC produce immune tolerance by activating selective Toll-like receptors (TLRs) in monocytes ( 96 ). TLRs, which are the most recognized family of pattern-recognition receptors (PRRs), which are a group of molecular pattern receptors related to pathogens ( 96 ).…”

Section: Immune Regulation Induced By Pancreas-related Microorganismsmentioning

confidence: 99%

“…Microorganisms in PDAC produce immune tolerance by activating selective Toll-like receptors (TLRs) in monocytes ( 96 ). TLRs, which are the most recognized family of pattern-recognition receptors (PRRs), which are a group of molecular pattern receptors related to pathogens ( 96 ). These receptors play a role in the immune response of microbial infections and accelerate tumorigenesis via innate and adaptive immune suppression in PDAC.…”

Section: Immune Regulation Induced By Pancreas-related Microorganismsmentioning

confidence: 99%

Research Progress of Pancreas-Related Microorganisms and Pancreatic Cancer

Zhang

et al. 2021

Front. Oncol.

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Pancreatic cancer is one of the most common digestive system cancers. Early diagnosis is difficult owing to the lack of specific symptoms and reliable biomarkers. The cause of pancreatic cancer remains ambiguous. Smoking, drinking, new-onset diabetes, and chronic pancreatitis have been proven to be associated with the occurrence of pancreatic cancer. In recent years, a large number of studies have clarified that a variety of microorganisms colonized in pancreatic cancer tissues are also closely related to the occurrence and development of pancreatic cancer, and the specific mechanisms include inflammatory induction, immune regulation, metabolism, and microenvironment changes caused by microorganism. The mechanism of action of the pancreatic colonized microbiome in the tumor microenvironment, as well as immunotherapy approaches require further study in order to find more evidence to explain the complex relationship between the pancreatic colonized microbiome and PDAC. Relevant studies targeting the microbiome may provide insight into the mechanisms of PDAC development and progression, improving treatment effectiveness and overall patient prognosis. In this article, we focus on the research relating to the microorganisms colonized in pancreatic cancer tissues, including viruses, bacteria, and fungi. We also highlight the microbial diversity in the occurrence, invasion, metastasis, treatment, and prognosis of pancreatic cancer in order to elucidate its significance in the early diagnosis and new therapeutic treatment of pancreatic cancer, which urgently need to be improved in clinical practice. The elimination or increase in diversity of the pancreatic microbiome is beneficial for prolonging the survival of PDAC patients, improving the response to chemotherapy drugs, and reducing tumor burden. The colonization of microorganisms in the pancreas may become a new hotspot in the diagnosis and treatment of pancreatic cancer.

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“…After exposure to invading microorganisms or tumor cells, TLRs on the surface of macrophages recognize antigens or components of microorganisms, such as lipopolysaccharide (LPS), and initiate defense signaling cascades. During this process, cytokines and chemokines increase to enhance antigen presentation and other immune responses [93]. CircRNAs carry out specific functions in this pathway.…”

Section: Circrna and Macrophagesmentioning

confidence: 99%

Circular RNA and tumor microenvironment

2020

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Circular RNAs (circRNAs) are small non-coding RNAs with a unique ring structure and play important roles as gene regulators. Disturbed expressions of circRNAs is closely related to varieties of pathological processes. The roles of circR-NAs in cancers have gained increasing concerns. The communications between the cancer cells and tumor microenvironment (TME) play complicated roles to affect the malignant behaviors of cancers, which potentially present new therapeutic targets. Herein, we reviewed the roles of circRNAs in the TME.

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Toll‐like receptors: A pathway alluding to cancer control

Cited by 28 publications

References 75 publications

Toll-Like Receptor 4 as a Favorable Prognostic Marker in Bladder Cancer: A Multi-Omics Analysis

Toll-Like Receptor 4 as a Favorable Prognostic Marker in Bladder Cancer: A Multi-Omics Analysis

Research Progress of Pancreas-Related Microorganisms and Pancreatic Cancer

Circular RNA and tumor microenvironment

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