Role of TLR4 as a prognostic factor for survival in various cancers: a meta-analysis

Hao, Bo; Chen, Zhe; Bi, Baochen; Yu, Miaomei; Yao, Shuang; Feng, Yuehua; Yu, Yang; Pan, Lili; Di, Dongmei; Luo, Guanghua; Zhang, Xiaoying

doi:10.18632/oncotarget.24178

Cited by 27 publications

(17 citation statements)

References 54 publications

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“…TLR4, the receptor for lipopolysaccharide (LPS), primarily induces inflammatory cytokines in immune cells,28 but it is also involved in carcinogenesis and cancer cell survival. Although TLR4 expression has been reported in a variety of tumors,8,9,11,29 TLR4 expression in patients with PTCL had not been studied. In the present study, we found that high expression of TLR4 was observed in 41.7% of all PTCL patients (60/144), and most frequently in patients with PTCL-NOS (58.8%) and ALK + ALCL (50.0%).…”

Section: Discussionmentioning

confidence: 99%

“…Initially, TLR4 expression was thought to be restricted to immune cells, but recent studies have shown that TLR4 is also highly expressed in some types of cancer cells, including colon cancer,6,7 pancreatic ductal adenocarcinoma,8 non-small cell lung cancer,9 and hepatocyte carcinoma 10. Some researchers have shown that high TLR4 expression is related to poor prognosis in malignant diseases,6,9,11 while others have failed to come to a similar conclusion 8. For PTCL, the significance of TLR4 expression has not been evaluated.…”

Section: Introductionmentioning

confidence: 99%

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<p>TLR4 expression correlated with PD-L1 expression indicates a poor prognosis in patients with peripheral T-cell lymphomas</p>

Song

Sun

Meng

et al. 2019

CMAR

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Background: Toll-like receptor 4 (TLR4), a member of the pattern recognition receptors, has been reported to be involved in carcinogenesis. However, the clinical impact of TLR4 in peripheral T-cell lymphomas (PTCL) remains unclear. Methods: The current study, using immunohistochemical staining, first examined TLR4 and programmed cell death-ligand 1 (PD-L1) expression in patients with PTCL, to correlate TLR4 and PD-L1 expression with clinicopathological parameters. Results: It was found that the rates of high expression of TLR4 and PD-L1 were 41.7% and 45.8%, respectively. TLR4 expression was closely associated with PD-L1 expression. The expression of TLR4 was closely related to primary extranodal site involvement, increased Ann Arbor stage, and low hemoglobin expression, while the expression of PD-L1 was closely related to a low platelet count and multiple extranodal organ involvements (>1). High expression of either TLR4 or PD-L1 indicated a poor survival rate for patients with PTCL. Multivariate analyses further confirmed that increased expression levels of TLR4 and PD-L1 are unfavorable prognostic factors for PTCL. Conclusion: This study demonstrates that the expressions of TLR4 and PD-L1 are independent predictors of survival time for patients with PTCL. Thus, TLR4 and PD-L1 may serve as potential therapeutic targets in PTCL patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

<p>TLR4 expression correlated with PD-L1 expression indicates a poor prognosis in patients with peripheral T-cell lymphomas</p>

Song

Sun

Meng

et al. 2019

CMAR

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“…Moreover, the majority of clinical studies showed that TLR4 expression strongly correlates with poor prognosis due to increased tumor size [72], stage [73], loss of differentiation [74], chemoresistance [73,75], venous invasion [72], lymph node metastasis [72,[75][76][77][78], recurrence [79], and shorter patient survival [77,80] (Table 1). A recently published meta-analysis examining data from 15 independent encompassing analyses of different tumors from 1294 patients found strong associations (P-values 0.001-0.05) between TLR4 expression and reduced overall and disease-free survival [81]. Collectively, these studies demonstrate high expression of TLR4 in a variety of human solid tumors suggesting it plays a prominent role in inflammation-fueled cancer progression and metastasis.…”

Section: Tlr4 Expression In Malignant Tumorsmentioning

confidence: 88%

TLR4-Induced Inflammation Is a Key Promoter of Tumor Growth, Vascularization, and Metastasis

Ran¹,

Bhattarai²,

Patel³

et al. 2020

Translational Studies on Inflammation

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Toll-like receptor-4 (TLR4) is a powerful pathway best known for inducing inflammation in response to bacteria-produced lipopolysaccharide. TLR4 is also activated by endogenous ligands produced by host-damaged cells and a chemo-drug paclitaxel. Under normal conditions, TLR4 is expressed mainly in macrophages and, at a lower level, in epithelial, endothelial, and stromal cells. Activated TLR4 significantly increases inflammatory cytokines and enhances cell proliferation, migration, invasion, and survival. While these functions in normal cells are essential for host defense and tissue repair, TLR4 overexpression in malignant cells promotes tumor growth and metastasis. This is because pro-oncogenic effects of activated TLR4 in tumor cells are amplified by similar event in TLR4-positive tumor-associated cells including endothelial cells and their mobilized progenitors. The collective activation of multiple cell types within the tumor promotes chemoresistance and metastasis. Here, we summarize the current knowledge of the TLR4 pathway and its functional outcomes in normal and tumor cells. We also discuss its underappreciated role in supporting tumor progression through vascular activation and recruitment of endothelial progenitors. The review considers several open questions regarding the impact of TLR4-mediated pro-and antitumor effects, structural requirements for recognition of the TLR4 complex, and a potential contribution of chemotherapy to tumor spread.

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“…On the other hand, we observed that pioglitazone reversed the proliferative effect of LPS on B16F10 cells in all concentrations. The effect of TLR4 on cancer progression has been shown in prostate, 28 breast, 29 ovarian 30 and lung cancer 31 and it is upregulated in different cancer cells. Activation of TLR4 can inhibit melanoma cell death while TLR4 inhibition led to inhibition of their survival.…”

Section: Discussionmentioning

confidence: 99%

Activation of PPARγ Inhibits TLR4 Signal Transduction Pathway in Melanoma Cancer In Vitro

2020

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Purpose : Although peroxisome proliferator-activated receptor γ (PPARγ) is known as a regulator of fatty acid storage, fat cell differentiation, glucose and lipid metabolism, recent studies show that PPARγ has anticancer effects. The mechanisms of PPARγ activation in melanoma cancer remain unclarified. Recently, increased TLR4 expression has been associated with the melanoma cancer progression. We investigated whether the anti-cancer effect of PPARγ is through regulating TLR4 signaling pathway. Methods: Mouse melanoma cells (B16F10) were treated in different groups: control, pioglitazone (1, 10, 100, 300 µmol/L), lipopolysaccharide (LPS) (5 µg/mL) and LPS + pioglitazone. In another experiment, they were treated with CLI-095 (1 μM), and after 1 hour pioglitazone was added and subsequently stimulated with LPS. MTT assay was performed to measure the cell viability in vitro. The expression of Tlr4, Myd88, Nf-κb genes were evaluated by quantitative reverse transcription PCR (qRT-PCR) in different groups. The concentration of tumor necrosis factor alpha and Interleukin 1 beta in the cell culture medium were measured by enzyme-linked immunosorbent assay (ELISA) kits. Results: We show that activation of PPARγ by its agonist, pioglitazone, reduces cell proliferation, Tlr-4, Myd-88, Nf-kb mRNA expression, and tumor necrosis factor-alpha (TNF-α) production but not interleukin-1 β (IL-1β) in B16F10 LPS–stimulated cells in vitro. Moreover, treatment of B16F10 cells with TLR4 inhibitor prior treatment with pioglitazone indicate that the anticancer effects of pioglitazone on melanoma cells was dependent on TLR4. Conclusion: The results indicate that pioglitazone has a beneficial protective effect against melanoma by affecting the TLR4 signaling pathway.

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Role of TLR4 as a prognostic factor for survival in various cancers: a meta-analysis

Cited by 27 publications

References 54 publications

<p>TLR4 expression correlated with PD-L1 expression indicates a poor prognosis in patients with peripheral T-cell lymphomas</p>

<p>TLR4 expression correlated with PD-L1 expression indicates a poor prognosis in patients with peripheral T-cell lymphomas</p>

TLR4-Induced Inflammation Is a Key Promoter of Tumor Growth, Vascularization, and Metastasis

Activation of PPARγ Inhibits TLR4 Signal Transduction Pathway in Melanoma Cancer In Vitro

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