{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:29:45Z","timestamp":1790126985488,"version":"4.0.1"},"reference-count":121,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education and Research","award":["LR11IPT04"],"award-info":[{"award-number":["LR11IPT04"]}]},{"name":"Ministry of Higher Education and Research","award":["LR16IPT04"],"award-info":[{"award-number":["LR16IPT04"]}]},{"name":"Institut Pasteur de Tunis","award":["LR11IPT04"],"award-info":[{"award-number":["LR11IPT04"]}]},{"name":"Institut Pasteur de Tunis","award":["LR16IPT04"],"award-info":[{"award-number":["LR16IPT04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells12010152","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T03:14:28Z","timestamp":1672370068000},"page":"152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["TLR9 and Glioma: Friends or Foes?"],"prefix":"10.3390","volume":"12","author":[{"given":"Emna","family":"Fehri","sequence":"first","affiliation":[{"name":"HPV Unit Research, Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases, Pasteur Institute of Tunis, Tunis 1002, Tunisia"},{"name":"Department of Human and Experimental Pathology, Pasteur Institute of Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emna","family":"Ennaifer","sequence":"additional","affiliation":[{"name":"HPV Unit Research, Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases, Pasteur Institute of Tunis, Tunis 1002, Tunisia"},{"name":"Department of Human and Experimental Pathology, Pasteur Institute of Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahima","family":"Bel Haj Rhouma","sequence":"additional","affiliation":[{"name":"HPV Unit Research, Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases, Pasteur Institute of Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9016-8987","authenticated-orcid":false,"given":"Monia","family":"Ardhaoui","sequence":"additional","affiliation":[{"name":"HPV Unit Research, Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases, Pasteur Institute of Tunis, Tunis 1002, Tunisia"},{"name":"Department of Human and Experimental Pathology, Pasteur Institute of Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Boubaker","sequence":"additional","affiliation":[{"name":"Department of Human and Experimental Pathology, Pasteur Institute of Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0140-6736(03)12328-8","article-title":"Primary brain tumours in adults","volume":"361","author":"Behin","year":"2003","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1158\/1055-9965.EPI-14-0275","article-title":"Epidemiologic and Molecular Prognostic Review of Glioblastoma","volume":"23","author":"Thakkar","year":"2014","journal-title":"Cancer Epidemiol. 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