The role of Toll-like receptor 9 in gynecologic cancer

Fehri, Emna; Ennaifer, Emna; Rhouma, Rahima Bel Haj; Guizani-Tabbane, Lamia; Guizani, Ikram; Boubaker, Samir

doi:10.1016/j.retram.2016.01.010

Cited by 12 publications

(8 citation statements)

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“…In our study, we found that TLR9 was hardly expressed compared to the other TLR genes, which led to TLR9 showing less correlation with both immune and stromal scores. However, several studies have reported that TLR9 is associated with the development of cancers, especially gynecologic cancer [ 36 , 37 ]. The activation of TLR9 on DCs and plasmacytoid DCs promotes the secretion of a large amount of type I IFN, which has both direct (tumor cell inhibitory effect) and indirect (antitumor immune responses) effects on cancer cells and is most evident in the early stages of antitumor immune responses [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Bioinformatics Analysis of Toll-Like Receptors (TLRs) in Pan-Cancer

Ping

Hong

Yang

et al. 2022

BioMed Research International

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Background. To conduct a comprehensive bioinformatics analysis on the transcriptome signatures of Toll-like receptors (TLRs) in pan-cancer. Materials and methods. A total of 11,057 tissues consisting of 33 types of carcinoma in The Cancer Genome Atlas (TCGA) were retrieved, and then we further explored the correlation between TLRs’ expression with tumorigenesis, immune infiltration, and drug sensitivity. We conducted a comprehensive bioinformatics analysis on TLR1 to 10 in pan-cancer, including differential expression analysis between normal and tumor tissues, differential immune subtype correlation, survival analysis, tumor immune infiltration estimating, stemness indices correlation, and drug responses correlation. Results. TLR2 was highly expressed in most types of tumors. TLR9 was hardly expressed compared to other TLR genes, which lead to TLR9 showing less correlation with both immune-estimate scores and stromal-estimate scores. All the TLRs were related with immune subtype of tumor samples that all of them were differentially expressed in differential immune subtype samples. The expression of TLRs was positively related with immune-estimate scores and stromal-estimate scores in almost all types of tumor. The expression of TLRs was negatively correlated with mRNA expression-based stemness scores (RNAss) in nearly almost type of tumors except kidney renal clear cell carcinoma (KIRC) and also negatively correlated with DNA methylation-based stemness scores (DNAss) in many types of tumors except adrenocortical carcinoma (ACC), cholangiocarcinoma (CHOL), KIRC, acute myeloid leukemia (LAML), low-grade glioma (LGG), testicular germ cell tumors (TGCT), thyroid carcinoma (THCA), thymoma (THYM), and uveal melanoma (UVM). The expression of TLR9 was significantly positively correlated with the drug sensitivity of fluphenazine, alectinib, carmustine, and 7−hydroxystaurosporine. TLR7 was significantly positively correlated with the drug sensitivity of alectinib. Conclusions. Our study reveals the significant role of TLRs family in pan-cancer and provides potential therapeutic strategies of cancer.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Bioinformatics Analysis of Toll-Like Receptors (TLRs) in Pan-Cancer

Ping

Hong

Yang

et al. 2022

BioMed Research International

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“…showed less correlation with both immune scores and stromal scores. But several studies have reported TLR9 were associated with the development of cancer, such as gynecologic cancer [33,34]. The activation of TLR9 on DC and pDC promotes the secretion of a large amount of type I IFN, which has direct (tumor cell inhibitory effect) and indirect (antitumor immune responses) effects on cancer cells, and is most obvious in the early stage of anti-tumor immune response [35].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Bioinformatics Analysis of Toll-like Receptors (TLRs) in Pan-Cancer

Ping

Hong

Yang

et al. 2021

Preprint

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Background: To conduct a comprehensive bioinformatics analysis on the transcriptome signatures of Toll-like receptors (TLRs) in pan-cancer. Materials and methods: A total of 11,057 tissues consisted of 33 types carcinoma in the cancer genome atlas (TCGA) were retrieved and then we further explored the correlation between TLRs’ expression with tumorigenesis, immune infiltration, and drug sensitivity. We conducted a comprehensive bioinformatics analysis on TLR1 to 10 in pan-cancer, including differential expression analysis between normal and tumor tissues, differential immune subtype correlation, survival analysis, tumor immune infiltration estimating, stemness indices correlation, and drug responses correlation.Results: TLR2 was high expressed in most type of tumors. TLR9 was hardly expressed compared to other TLR genes, which lead to TLR9 showed less correlation with both immune-estimate scores and stromal-estimate scores. All the TLRs were related with immune subtype of tumor samples that all of them were differentially expressed in differential immune subtype samples. Expression of TLRs were positively related with immune-estimate scores and stromal-estimate scores in almost all types of tumor. Expression of TLRs were negatively correlated with mRNA expression based stemness scores (RNAss) in nearly almost type of tumors except kidney renal clear cell carcinoma (KIRC), and also negatively correlated with DNA methylation based stemness scores (DNAss) in many types of tumors except Adrenocortical carcinoma (ACC), cholangiocarcinoma (CHOL), KIRC, acute myeloid leukemia (LAML), low-grade glioma (LGG), Testicular Germ Cell Tumors (TGCT), Thyroid carcinoma (THCA), Thymoma (THYM), and Uveal Melanoma (UVM). The expression of TLR9 was significant positively correlated with the drug sensitivity of Fluphenazine, Alectinib, Carmustine, and 7−Hydroxystaurosporine. TLR7 was significant positively correlated with the drug sensitivity of Alectinib.Conclusions: Our study reveals the significant role of TLRs family in pan-cancer and provides potential therapeutic strategies of cancer.

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“…This TLR9 agonist seems to work in synergy with inhibitors of VEGF receptors such as everolimus by increasing the effect on reducing angiogenesis and tumor growth (Damiano et al, 2013). In gynecological cancers, TLR9 seems to help in tumor regression by induction of cytotoxic T cell response reducing the numbers of myeloid-derived suppressor cells, the tumor-associated macrophages, and the regulatory T cells (Fehri et al, 2016). Human lung cancer cells appear to be sensitized to radiation, through the activation of TLR9 via p53 signaling (Yuan et al, 2018).…”

Section: Inhibition Of Cancer By Tlr Agonistsmentioning

confidence: 99%

Toll‐like receptors: A pathway alluding to cancer control

Ayala-Cuellar

Cho

Choi

2019

Journal Cellular Physiology

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Toll-like receptors (TLRs) are usually expressed on immune cells such as macrophages, dendritic cells, mast cells, as well as on eosinophils and some epithelial cells. They play a central role in the recognition of harmful molecules that belong to invading microorganisms or internal damaged tissues, which lead to inflammation.Among the hallmarks of cancer, there is immune evasion and inflammation. Summing this with the discovery that a majority of cancers also seem to express TLRs, made researchers realize these receptors might also be linked with cancer progression. This review will cover some of the effects of TLR engagement in cancer cells that might induce the promotion or inhibition of cancer with mechanisms involved. The differences of TLR expression in cancer progression and its possible relation with patient prognosis, TLR genetic disorders found in cancer, and new strategies to cancer therapy will be discussed to target TLRs in cancer cells.

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The role of Toll-like receptor 9 in gynecologic cancer

Cited by 12 publications

References 50 publications

Comprehensive Bioinformatics Analysis of Toll-Like Receptors (TLRs) in Pan-Cancer

Comprehensive Bioinformatics Analysis of Toll-Like Receptors (TLRs) in Pan-Cancer

Comprehensive Bioinformatics Analysis of Toll-like Receptors (TLRs) in Pan-Cancer

Toll‐like receptors: A pathway alluding to cancer control

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