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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Main Authors: Emna Fehri, Emna Ennaifer, Rahima Bel Haj Rhouma, Monia Ardhaoui, Samir Boubaker
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Cells
Subjects:
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.
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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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