TLR9 and Glioma: Friends or Foes?
Toll-like receptor 9 (TLR9) is an intracellular innate immunity receptor that plays a vital role in chronic inflammation and in recognizing pathogenic and self-DNA in immune complexes. This activation of intracellular signaling leads to the transcription of either immune-related or malignancy genes...
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MDPI AG
2022-12-01
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Series: | Cells |
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Online Access: | https://www.mdpi.com/2073-4409/12/1/152 |
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author | Emna Fehri Emna Ennaifer Rahima Bel Haj Rhouma Monia Ardhaoui Samir Boubaker |
author_facet | Emna Fehri Emna Ennaifer Rahima Bel Haj Rhouma Monia Ardhaoui Samir Boubaker |
author_sort | Emna Fehri |
collection | DOAJ |
description | Toll-like receptor 9 (TLR9) is an intracellular innate immunity receptor that plays a vital role in chronic inflammation and in recognizing pathogenic and self-DNA in immune complexes. This activation of intracellular signaling leads to the transcription of either immune-related or malignancy genes through specific transcription factors. Thus, it has been hypothesized that TLR9 may cause glioma. This article reviews the roles of TLR9 in the pathogenesis of glioma and its related signaling molecules in either defending or promoting glioma. TLR9 mediates the invasion-induced hypoxia of brain cancer cells by the activation of matrix metalloproteinases (2, 9, and 13) in brain tissues. In contrast, the combination of the TLR9 agonist CpG ODN to radiotherapy boosts the role of T cells in antitumor effects. The TLR9 agonist CpG ODN 107 also enhances the radiosensitivity of human glioma U87 cells by blocking tumor angiogenesis. CpG enhances apoptosis in vitro and in vivo. Furthermore, it can enhance the antigen-presenting capacity of microglia, switch immune response toward CD8 T cells, and reduce the number of CD4CD25 Treg cells. CpG ODN shows promise as a potent immunotherapeutic drug against cancer, but specific cautions should be taken when activating TLR9, especially in the case of glioblastoma. |
first_indexed | 2024-03-11T10:05:01Z |
format | Article |
id | doaj.art-7eb74cc0ccef46fdad7974bcdc301354 |
institution | Directory Open Access Journal |
issn | 2073-4409 |
language | English |
last_indexed | 2024-03-11T10:05:01Z |
publishDate | 2022-12-01 |
publisher | MDPI AG |
record_format | Article |
series | Cells |
spelling | doaj.art-7eb74cc0ccef46fdad7974bcdc3013542023-11-16T15:06:47ZengMDPI AGCells2073-44092022-12-0112115210.3390/cells12010152TLR9 and Glioma: Friends or Foes?Emna Fehri0Emna Ennaifer1Rahima Bel Haj Rhouma2Monia Ardhaoui3Samir Boubaker4HPV Unit Research, Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases, Pasteur Institute of Tunis, Tunis 1002, TunisiaHPV Unit Research, Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases, Pasteur Institute of Tunis, Tunis 1002, TunisiaHPV Unit Research, Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases, Pasteur Institute of Tunis, Tunis 1002, TunisiaHPV Unit Research, Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases, Pasteur Institute of Tunis, Tunis 1002, TunisiaDepartment of Human and Experimental Pathology, Pasteur Institute of Tunis, Tunis 1002, TunisiaToll-like receptor 9 (TLR9) is an intracellular innate immunity receptor that plays a vital role in chronic inflammation and in recognizing pathogenic and self-DNA in immune complexes. This activation of intracellular signaling leads to the transcription of either immune-related or malignancy genes through specific transcription factors. Thus, it has been hypothesized that TLR9 may cause glioma. This article reviews the roles of TLR9 in the pathogenesis of glioma and its related signaling molecules in either defending or promoting glioma. TLR9 mediates the invasion-induced hypoxia of brain cancer cells by the activation of matrix metalloproteinases (2, 9, and 13) in brain tissues. In contrast, the combination of the TLR9 agonist CpG ODN to radiotherapy boosts the role of T cells in antitumor effects. The TLR9 agonist CpG ODN 107 also enhances the radiosensitivity of human glioma U87 cells by blocking tumor angiogenesis. CpG enhances apoptosis in vitro and in vivo. Furthermore, it can enhance the antigen-presenting capacity of microglia, switch immune response toward CD8 T cells, and reduce the number of CD4CD25 Treg cells. CpG ODN shows promise as a potent immunotherapeutic drug against cancer, but specific cautions should be taken when activating TLR9, especially in the case of glioblastoma.https://www.mdpi.com/2073-4409/12/1/152TLR9gliomatumor regressiontumor progressiondichotomic role |
spellingShingle | Emna Fehri Emna Ennaifer Rahima Bel Haj Rhouma Monia Ardhaoui Samir Boubaker TLR9 and Glioma: Friends or Foes? Cells TLR9 glioma tumor regression tumor progression dichotomic role |
title | TLR9 and Glioma: Friends or Foes? |
title_full | TLR9 and Glioma: Friends or Foes? |
title_fullStr | TLR9 and Glioma: Friends or Foes? |
title_full_unstemmed | TLR9 and Glioma: Friends or Foes? |
title_short | TLR9 and Glioma: Friends or Foes? |
title_sort | tlr9 and glioma friends or foes |
topic | TLR9 glioma tumor regression tumor progression dichotomic role |
url | https://www.mdpi.com/2073-4409/12/1/152 |
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