Expression profile of Toll‑like receptors in human breast cancer

Shi, Shuxun; Xu, Cong; Fang, Xiaonan; Zhang, Yonghuan; Li, Hua; Wen, Wujun

doi:10.3892/mmr.2019.10853

Cited by 40 publications

(39 citation statements)

References 36 publications

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“…TLR3 has been reported to express on normal epithelial cells, such as lung tissue. The abnormal expression of TLR3 has been reported on various of cancer tissues ( 10 , 11 ). TLR3 has also been recognized as a favorable prognosis biomarker of lung cancer by activating apoptosis or promoting autophagy ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma

Tian

et al. 2021

Front. Oncol.

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This study aims to analyze the methylation regulation of TLR3 in lung adenocarcinoma (LUAD) and to explore the association of TLR3 expression with immune microenvironment. TLR3 has a decreased expression in LUAD tissues and low expression of TLR3 is not only associated with poor prognosis in patients with LUAD, but also can be used as a diagnostic marker. Bisulfite sequencing PCR (BSP) results showed that the methylation level in the promoter of TLR3 was negatively correlated with the level of TLR3 mRNA in LUAD tissues. TIMER analysis showed that TLR3 was negatively correlated with the tumor purity of LUAD and positively with immune cell infiltration to some extent. ESTIMATE analysis also suggested that TLR3 expression and its methylation had significant correlation with immune score. The lower immune scores were associated with the late stage of LUAD and poor prognosis. The high expression of TLR3 might inhibit the development of LUAD by activating apoptosis pathway. The proteins interacted with TLR3 were mainly involved in the apoptosis pathway and positively correlated with the key genes (MYD88, Caspase 8, BIRC3, PIK3R1) in this pathway. Therefore, TLR3 as a key biomarker for prognosis and diagnosis in LUAD, might be considered as a potential epigenetic and immunotherapeutic target.

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Section: Introductionmentioning

confidence: 99%

Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma

Tian

et al. 2021

Front. Oncol.

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“…Activation of TLR8 signaling could enhance anti-tumor immunity by reversing the inhibition of tumor-specific T cells in lung cancer 41 and identify purified H. pylori RNA to induce inflammatory response in gastric cancer 42 . Moreover, TLR8 had positive correlation with IFN-β in breast cancer 43 and could activate M1-like macrophages to disrupt platinum resistance in colorectal cancer 44 . IL-7 was a cytokine, primarily regarding its effects on T-cells and B-cells.…”

Section: Discussionmentioning

confidence: 98%

Integrated analysis identifies AQP9 correlates with immune infiltration and acts as a prognosticator in multiple cancers

Liu

et al. 2020

Sci Rep

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Aquaporin 9 (AQP9), as an aquaglyceroporin, is expressed in many immune cells and plays important role in tumor initiation and progression. However, the relationship between AQP9 and tumor-infiltrating cells, and its prognostic value in cancers still require comprehensive understanding. Herein, we aimed to elucidate the correlations of AQP9 with prognosis and immune infiltration levels in diverse cancers. We detected the expression and survival data of AQP9 through Oncomine, TIMER, Kaplan–Meier Plotter and PrognoScan databases. The correlations between AQP9 and immune infiltrates were analyzed in TIMER database. Our results found that high AQP9 expression was significantly correlated with worse prognosis in breast, colon and lung cancers, while predicted better prognosis in gastric cancer. Moreover, AQP9 had significant association with various immune infiltrating cells including CD8+ and CD4+ T cells, neutrophils, macrophages and dendritic cells (DCs), and diverse immune gene markers in BRCA, COAD, LUAD, LUSC and STAD. AQP9 was also significantly correlated with the regulation of tumor associated macrophages (TAM). These results indicate that AQP9 can play as a significant biomarker to determine the prognosis and the immune infiltrating levels in different cancers. It might also contribute to the development of the immunotherapy in breast, colon, lung and gastric cancers.

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“…We previously showed that IMO-2125 has a strong in vivo activity in colorectal and pancreatic cancer models by interfering with EGFRrelated signaling and synergizing with cetuximab 14 15 and with anti-VEGF monoclonal antibody bevacizumab. 16 Different studies report TLR9 expression in both cancer and immune cells [31][32][33][34] and its potential ability to enhance the effect of current immunotherapy. 35 36 Immunotherapy revolutionized treatment of several cancers with high degree of T-cell infiltration (hot tumors), whereas low efficacy was reported in tumors with low levels of T-cell infiltration (cold tumors).…”

Section: Discussionmentioning

confidence: 99%

Intratumoral injection of TLR9 agonist promotes an immunopermissive microenvironment transition and causes cooperative antitumor activity in combination with anti-PD1 in pancreatic cancer

Carbone

Piro

Agostini

et al. 2021

J Immunother Cancer

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BackgroundComplex tumor and immune microenvironment render pancreatic ductal adenocarcinoma (PDAC) resistant to immune checkpoint inhibitors (ICIs). Therefore, a strategy to convert the immune hostile into an immunopermissive tumor is required. Recent studies showed that intratumoral injection of Toll-like receptor 9 agonist IMO-2125 primes the adaptive immune response. Phase I and II trials with intratumoral IMO-2125 demonstrated its safety and antitumoral activity.MethodsWe generated an array of preclinical models by orthotopically engrafting PDAC-derived cell lines in syngeneic mice and categorized them as high, low and no immunogenic potential, based on the ability of tumor to evoke T lymphocyte or NK cell response. To test the antitumor efficacy of IMO-2125 on locally treated and distant sites, we engrafted cancer cells on both flanks of syngeneic mice and treated them with intratumoral IMO-2125 or vehicle, alone or in combination with anti-PD1 ICI. Tumor tissues and systemic immunity were analyzed by transcriptomic, cytofluorimetric and immunohistochemistry analysis.ResultsWe demonstrated that intratumoral IMO-2125 as single agent triggers immune system response to kill local and distant tumors in a selected high immunogenic subtype affecting tumor growth and mice survival. Remarkably, intratumoral IMO-2125 in combination with systemic anti-PD1 causes a potent antitumor effect on primary injected and distant sites also in pancreatic cancer models with low immunogenic potential, preceded by a transition toward an immunopermissive microenvironment, with increase in tumor-infiltrating dendritic and T cells in tumor and lymph nodes.ConclusionWe demonstrated a potent antitumor activity of IMO-2125 and anti-PD1 combination in immunotherapy-resistant PDAC models through the modulation of immune microenvironment, providing the rationale to translate this strategy into a clinical setting.

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Expression profile of Toll‑like receptors in human breast cancer

Cited by 40 publications

References 36 publications

Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma

Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma

Integrated analysis identifies AQP9 correlates with immune infiltration and acts as a prognosticator in multiple cancers

Intratumoral injection of TLR9 agonist promotes an immunopermissive microenvironment transition and causes cooperative antitumor activity in combination with anti-PD1 in pancreatic cancer

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