Toll‐like receptors 3, 4 and 9 in hepatocellular carcinoma: Relationship with clinicopathological characteristics and prognosis

Eiró, Noemí; Altadill, Antonio; Juarez, L. Morales; Rodrı́guez, Manuel; González, Luis O.; Atienza, Sara; Bermúdez, Sandra; Fernández-García, Belén; Fresno-Forcelledo, Manuel F; Rodrigo, Luís

doi:10.1111/hepr.12180

Cited by 65 publications

(38 citation statements)

References 43 publications

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“…Conversely, expression of TLR4 on stromal fibroblasts was associated with poor prognosis in colorectal cancer14. Similar data were reported for hepatocellular carcinoma, where TLR9 expression on tumour-associated fibroblasts was associated with reduced overall survival50. Thus, our study is one of the first to experimentally demonstrate a role for radioresistant (stromal) cells in regulation of tumour progression via endosomal TLR signalling.…”

Section: Discussionsupporting

confidence: 84%

Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth

et al. 2017

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Toll-like receptors (TLRs) are located either on the cell surface or intracellularly in endosomes and their activation normally contributes to the induction of protective immune responses. However, in cancer their activation by endogenous ligands can modulate tumour progression. It is currently unknown how endosomal TLRs regulate endogenous anti-tumour immunity. Here we show that TLR3, 7 and 9 deficiencies on host cells, after initial tumour growth, result in complete tumour regression and induction of anti-tumour immunity. Tumour regression requires the combined absence of all three receptors, is dependent on both CD4 and CD8 T cells and protects the mice from subsequent tumour challenge. While tumours in control mice are infiltrated by higher numbers of regulatory T cells, tumour regression in TLR-deficient mice is paralleled by altered vascular structure and strongly induced influx of cytotoxic and cytokine-producing effector T cells. Thus, endosomal TLRs may represent a molecular link between the inflamed tumour cell phenotype, anti-tumour immunity and the regulation of T-cell activation.

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Section: Discussionsupporting

confidence: 84%

Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth

et al. 2017

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“…It is therefore of great importance to better define the function of each TLR expressed on a wide range of tumor cells. Many reports have described that HCC tumor cells from patients express TLR3 and TLR9, which are both associated with the prognosis of HCC [26]; moreover, HCC-derived cell lines are positive for both TLR3 and TLR9 [16,17,27]. Both cell-surface and cytoplasmic TLR3 expressions have been observed in HCC cells [20]; TLR9 is mainly expressed on endosomes, but cell-surface expression of TLR9 has also been observed on HCCs [28].…”

Section: Discussionmentioning

confidence: 99%

Phosphorothioate modification of the TLR9 ligand CpG ODN inhibits poly(I:C)-induced apoptosis of hepatocellular carcinoma by entry blockade

et al. 2014

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“…Ultimately, 24 studies11–14,18–38 were included in our analysis, with four of them investigated two or three TLRs synchronously. Among them, 12,11–13,18–26 five,13,14,27–29 and eleven13,18,30–38 studies focused on TLR4, TLR7, and TLR9, respectively. The flow diagram of the study selection process is shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

Prognostic role of Toll-like receptors in cancer: a meta-analysis

Wang¹,

Zhang²,

Xiao³

et al. 2018

TCRM

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BackgroundRecent studies have shown that Toll-like receptors (TLRs) may be associated with cancers. The aim of this meta-analysis is to summarize the predicting role of TLRs for survival in patients with a variety of carcinomas.Materials and methodsEligible studies were identified and assessed for quality through multiple search strategies. We collected data from studies investigating the relationship between the expression level of TLRs and survival in cancer patients. Studies were pooled and combined hazard ratios (HRs) of TLRs for survival were analyzed.ResultsA total of 24 studies, including 2,812 patients with various cancers, were identified for the meta-analysis. Importantly, this meta-analysis showed that higher expression levels of TLR4 or TLR7 in tumor tissues could predict poorer survival, with the pooled HR being 1.29 (95% CI: 1.17, 1.42) and 1.71 (95% CI: 1.38, 2.12), respectively. However, higher expression of TLR9 had no significant association with outcome as HR was 0.84 (95% CI: 0.62, 1.115). Heterogeneity existed in TLR4 and TLR9 studies (P-value <0.001) but not in TLR7 studies (P-value >0.05).ConclusionThe expression level of TLR4 or TLR7 in cancerous tissue may have a prognosis value in patients with various cancers.

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Toll‐like receptors 3, 4 and 9 in hepatocellular carcinoma: Relationship with clinicopathological characteristics and prognosis

Abstract: The results demonstrated an association between TLR3, TLR4 and TLR9 expression and tumor aggressiveness and poor prognosis in HCC.

Cited by 65 publications

References 43 publications

Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth

Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth

Phosphorothioate modification of the TLR9 ligand CpG ODN inhibits poly(I:C)-induced apoptosis of hepatocellular carcinoma by entry blockade

Prognostic role of Toll-like receptors in cancer: a meta-analysis

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