TLR9 expression is associated with prognosis in patients with glioblastoma multiforme

Leng, Lige; Jiang, Tao; Zhang, Yazhou

doi:10.1016/j.jocn.2011.03.037

Cited by 22 publications

(17 citation statements)

References 38 publications

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“…TLR9 overexpression by cancer epithelial [35][36][37][38][39][40][41]. Results from our study are in agreement with those reported in the literature [42].…”

Section: Discussionsupporting

confidence: 93%

Biopathological Significance of TLR9 Expression in Cancer Cells and Tumor Microenvironment Across Invasive Breast Carcinomas Subtypes

Meseure

Vacher

Alsibai

et al. 2016

Cancer Microenvironment

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Toll-like receptors (TLRs) are pattern recognition receptors mainly expressed by cells of the immune system but also by epithelial tumor cells. Little is known about expression patterns of TLR genes in breast tumors, and their clinical significance is unclear. The aim of our study was to investigate expression of TLRs pathway components in pre-invasive breast lesions and invasive breast carcinomas (IBCs). We used RT-PCR assays to quantify mRNA levels of the 10 TLR genes and genes involved in TLR pathways in 350 breast tumors from patients with known clinical/pathological status and long-term outcome. Sets of 158 breast samples were also analyzed by immunochemistry including; 40 early noninvasive breast lesions, 38 IBCs and 80 triple negative carcinomas subtype (TNCs). We identified TLR9 as the major TLR gene family member upregulated in breast tumors and more particularly in TNCs. Immunohistochemical studies demonstrated that TLR9 protein was expressed in tumor epithelial and stromal cells of the TLR9 mRNA-overexpressing tumors. TLR9 overexpression appears very early during breast carcinogenesis. High TLR9 levels were associated with favorable outcome in the TNC sub-group. TLR9 overexpression was associated with alterations of down-stream components of the TLR9 signaling pathway, epithelio-mesenchymal transition (EMT) induction and EGFR pathway deregulation. TNCs with TLR9 overexpression were significantly correlated with development of a fibrous and inflammatory microenvironment with variable status of nuclear phosphoSTAT3. Our results suggest that TLR9 could play a role in TNC carcinogenesis and could be useful as predictive biomarker and therapeutic target.Keywords Toll-like receptor 9 . Breast cancer subtypes .

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“…TLR9 overexpression by cancer epithelial [35][36][37][38][39][40][41]. Results from our study are in agreement with those reported in the literature [42].…”

Section: Discussionsupporting

confidence: 93%

Biopathological Significance of TLR9 Expression in Cancer Cells and Tumor Microenvironment Across Invasive Breast Carcinomas Subtypes

Meseure

Vacher

Alsibai

et al. 2016

Cancer Microenvironment

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“…Furthermore, CpG/TLR9 and STAT3 form a feedforward loop in GSCs: CpG-TLR9 activates STAT3 while activated STAT3 upregulates TLR9 expression. These results provide a possible molecular explanation as to why TLR9 upregulation correlates with poor survival of some cancer patients including GBM patients (30, 31). …”

Section: Discussionmentioning

confidence: 76%

“…Elevated TLR9 expression has been shown to correlate with poor survival of malignant glioma patients (30, 31). We therefore tested TLR9 expression levels in GSC subpopulations of glioblastoma tumors.…”

Section: Resultsmentioning

confidence: 99%

“…The ligands of TLR9, CpG-ODNs, have been extensively studied in animal models and in clinical trials as cancer immunotherapeutics (25, 29). However, evidence has been accumulating that TLR9 can be elevated in tumors and associated with cancer progression (30, 31). Our results suggest that TLR9, an important inflammatory signaling molecule, is crucial for cancer stem cell development/maintenance in malignant glioma.…”

Section: Discussionmentioning

confidence: 99%

“…Our recent data further illustrate that silencing STAT3 in myeloid cells by CpG- STAT3siRNA resulted in antitumor effects at both primary tumor and future metastatic sites (14, 27, 28). While a role of TLR9 in stimulating immune responses has been recognized (21, 29), expression of TLR9 in tumors, including malignant glioma, correlates with poor patient survival (30, 31). TLR2 and TLR7 have also been shown to promote tumor growth in a STAT3-dependent manner (32).…”

Section: Introductionmentioning

confidence: 99%

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TLR9 Is Critical for Glioma Stem Cell Maintenance and Targeting

et al. 2014

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Understanding supports for cancer stem-like cells in malignant glioma may suggest therapeutic strategies for their elimination. Here we show that the Toll-like receptor TLR9 is elevated in glioma stem-like cells (GSC) where it contributes to glioma growth. TLR9 overexpression is regulated by STAT3 which was required for GSC maintenance. Stimulation of TLR9 with a CpG ligand (CpG ODN) promoted GSC growth, whereas silencing TLR9 expression abrogated GSC development. CpG-ODN treatment induced Frizzled4-dependent activation of JAK2, thereby activating STAT3. Targeted delivery of siRNA into GSC was achieved via TLR9 using CpG-siRNA conjugates. Through local or systemic treatment, administration of CpG-Stat3 siRNA to silence STAT3 in vivo reduced GSC along with glioma growth. Our findings identify TLR9 as a functional marker for GSC and a target for the delivery of efficacious therapeutics for glioma treatment.

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Tlr9

Lim¹

2017

Cancer Therapeutic Targets

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TLR9 expression is associated with prognosis in patients with glioblastoma multiforme

Cited by 22 publications

References 38 publications

Biopathological Significance of TLR9 Expression in Cancer Cells and Tumor Microenvironment Across Invasive Breast Carcinomas Subtypes

Biopathological Significance of TLR9 Expression in Cancer Cells and Tumor Microenvironment Across Invasive Breast Carcinomas Subtypes

TLR9 Is Critical for Glioma Stem Cell Maintenance and Targeting

Tlr9

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