{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T07:03:38Z","timestamp":1784185418685,"version":"3.55.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s00109-026-02702-9","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:05:45Z","timestamp":1784181945000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor-intrinsic TLR4 signaling as a context-dependent rheostat in glioblastoma"],"prefix":"10.1007","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1367-5157","authenticated-orcid":false,"given":"Thura Tun","family":"Oo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"issue":"10","key":"2702_CR1","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1056\/NEJMoa043330","volume":"352","author":"R Stupp","year":"2005","unstructured":"Stupp R, Mason Warren P, van den Bent Martin J, Weller M, Fisher B, Taphoorn Martin JB, Belanger K, Brandes Alba A, Marosi C, Bogdahn U, Curschmann J, Janzer Robert C, Ludwin Samuel K, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff Ren\u00e9 O (2005) Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N Engl J Med 352(10):987\u2013996. https:\/\/doi.org\/10.1056\/NEJMoa043330","journal-title":"N Engl J Med"},{"issue":"2","key":"2702_CR2","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s11060-009-9956-7","volume":"96","author":"JA van Genugten","year":"2010","unstructured":"van Genugten JA, Leffers P, Baumert BG, Tjon AFH, Twijnstra A (2010) Effectiveness of temozolomide for primary glioblastoma multiforme in routine clinical practice. J Neurooncol 96(2):249\u2013257. https:\/\/doi.org\/10.1007\/s11060-009-9956-7","journal-title":"J Neurooncol"},{"issue":"9","key":"2702_CR3","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1016\/j.jocn.2008.12.008","volume":"16","author":"AJ Gauden","year":"2009","unstructured":"Gauden AJ, Hunn A, Erasmus A, Waites P, Dubey A, Gauden SJ (2009) Combined modality treatment of newly diagnosed glioblastoma multiforme in a regional neurosurgical centre. J Clin Neurosci 16(9):1174\u20131179. https:\/\/doi.org\/10.1016\/j.jocn.2008.12.008","journal-title":"J Clin Neurosci"},{"issue":"6190","key":"2702_CR4","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1126\/science.1254257","volume":"344","author":"AP Patel","year":"2014","unstructured":"Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suv\u00e0 ML, Regev A, Bernstein BE (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344(6190):1396\u20131401. https:\/\/doi.org\/10.1126\/science.1254257","journal-title":"Science"},{"issue":"3","key":"2702_CR5","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.ccr.2013.08.001","volume":"24","author":"KPL Bhat","year":"2013","unstructured":"Bhat KPL, Balasubramaniyan V, Vaillant B, Ezhilarasan R, Hummelink K, Hollingsworth F, Wani K, Heathcock L, James JD, Goodman LD, Conroy S, Long L, Lelic N, Wang S, Gumin J, Raj D, Kodama Y, Raghunathan A, Olar A, Joshi K, Pelloski CE, Heimberger A, Kim SH, Cahill DP, Rao G, Den Dunnen WFA, Boddeke H, Phillips HS, Nakano I, Lang FF, Colman H, Sulman EP, Aldape K (2013) Mesenchymal differentiation mediated by NF-\u03baB promotes radiation resistance in glioblastoma. Cancer Cell 24(3):331\u2013346. https:\/\/doi.org\/10.1016\/j.ccr.2013.08.001","journal-title":"Cancer Cell"},{"issue":"6","key":"2702_CR6","doi-asserted-by":"publisher","first-page":"2609","DOI":"10.1111\/cas.15773","volume":"114","author":"H Wu","year":"2023","unstructured":"Wu H, Guo C, Wang C, Xu J, Zheng S, Duan J, Li Y, Bai H, Xu Q, Ning F, Wang F, Yang Q (2023) Single-cell RNA sequencing reveals tumor heterogeneity, microenvironment, and drug-resistance mechanisms of recurrent glioblastoma. Cancer Sci 114(6):2609\u20132621. https:\/\/doi.org\/10.1111\/cas.15773","journal-title":"Cancer Sci"},{"issue":"3","key":"2702_CR7","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1073\/pnas.1320611111","volume":"112","author":"M Meyer","year":"2015","unstructured":"Meyer M, Reimand J, Lan X, Head R, Zhu X, Kushida M, Bayani J, Pressey JC, Lionel AC, Clarke ID, Cusimano M, Squire JA, Scherer SW, Bernstein M, Woodin MA, Bader GD, Dirks PB (2015) Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity. Proc Natl Acad Sci U S A 112(3):851\u2013856. https:\/\/doi.org\/10.1073\/pnas.1320611111","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"2702_CR8","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1093\/brain\/awz202","volume":"142","author":"GZ Yi","year":"2019","unstructured":"Yi GZ, Huang G, Guo M, Zhang X, Wang H, Deng S, Li Y, Xiang W, Chen Z, Pan J, Li Z, Yu L, Lei B, Liu Y, Qi S (2019) Acquired temozolomide resistance in MGMT-deficient glioblastoma cells is associated with regulation of DNA repair by DHC2. Brain 142(8):2352\u20132366. https:\/\/doi.org\/10.1093\/brain\/awz202","journal-title":"Brain"},{"issue":"3","key":"2702_CR9","doi-asserted-by":"publisher","first-page":"eaar2766","DOI":"10.1126\/sciadv.aar2766","volume":"4","author":"FL Ricklefs","year":"2018","unstructured":"Ricklefs FL, Alayo Q, Krenzlin H, Mahmoud AB, Speranza MC, Nakashima H, Hayes JL, Lee K, Balaj L, Passaro C, Rooj AK, Krasemann S, Carter BS, Chen CC, Steed T, Treiber J, Rodig S, Yang K, Nakano I, Lee H, Weissleder R, Breakefield XO, Godlewski J, Westphal M, Lamszus K, Freeman GJ, Bronisz A, Lawler SE, Chiocca EA (2018) Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv 4(3):eaar2766. https:\/\/doi.org\/10.1126\/sciadv.aar2766","journal-title":"Sci Adv"},{"issue":"13","key":"2702_CR10","doi-asserted-by":"publisher","first-page":"4401","DOI":"10.1158\/1078-0432.Ccr-09-0155","volume":"15","author":"M Candolfi","year":"2009","unstructured":"Candolfi M, Yagiz K, Foulad D, Alzadeh GE, Tesarfreund M, Muhammad AK, Puntel M, Kroeger KM, Liu C, Lee S, Curtin JF, King GD, Lerner J, Sato K, Mineharu Y, Xiong W, Lowenstein PR, Castro MG (2009) Release of HMGB1 in response to proapoptotic glioma killing strategies: efficacy and neurotoxicity. Clin Cancer Res 15(13):4401\u20134414. https:\/\/doi.org\/10.1158\/1078-0432.Ccr-09-0155","journal-title":"Clin Cancer Res"},{"key":"2702_CR11","doi-asserted-by":"publisher","first-page":"620883","DOI":"10.3389\/fcell.2021.620883","volume":"9","author":"XY Gao","year":"2021","unstructured":"Gao XY, Zang J, Zheng MH, Zhang YF, Yue KY, Cao XL, Cao Y, Li XX, Han H, Jiang XF, Liang L (2021) Temozolomide Treatment Induces HMGB1 to Promote the Formation of Glioma Stem Cells via the TLR2\/NEAT1\/Wnt Pathway in Glioblastoma. Front Cell Dev Biol 9:620883. https:\/\/doi.org\/10.3389\/fcell.2021.620883","journal-title":"Front Cell Dev Biol"},{"key":"2702_CR12","doi-asserted-by":"publisher","unstructured":"Pasi F, Paolini A, Nano R, Di Liberto R, Capelli E (2014) Effects of single or combined treatments with radiation and chemotherapy on survival and danger signals expression in glioblastoma cell lines. BioMed Res Int 2014(1):453497. https:\/\/doi.org\/10.1155\/2014\/453497","DOI":"10.1155\/2014\/453497"},{"issue":"1","key":"2702_CR13","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1186\/s12967-024-05489-w","volume":"22","author":"H Qiu","year":"2024","unstructured":"Qiu H, Shao Z, Wen X, Qu D, Liu Z, Chen Z, Zhang X, Ding X, Zhang L (2024) HMGB1\/TREM2 positive feedback loop drives the development of radioresistance and immune escape of glioblastoma by regulating TLR4\/Akt signaling. J Translational Med 22(1):688. https:\/\/doi.org\/10.1186\/s12967-024-05489-w","journal-title":"J Translational Med"},{"key":"2702_CR14","doi-asserted-by":"publisher","first-page":"8916","DOI":"10.12659\/msm.912104","volume":"24","author":"P Cheng","year":"2018","unstructured":"Cheng P, Ma Y, Gao Z, Duan L (2018) High Mobility Group Box 1 (HMGB1) Predicts Invasion and Poor Prognosis of Glioblastoma Multiforme via Activating AKT Signaling in an Autocrine Pathway. Med Sci Monit 24:8916\u20138924. https:\/\/doi.org\/10.12659\/msm.912104","journal-title":"Med Sci Monit"},{"issue":"24","key":"2702_CR15","doi-asserted-by":"publisher","first-page":"21129","DOI":"10.1074\/jbc.M009164200","volume":"276","author":"J da Silva Correia","year":"2001","unstructured":"da Silva Correia J, Soldau K, Christen U, Tobias PS, Ulevitch RJ (2001) Lipopolysaccharide Is in Close Proximity to Each of the Proteins in Its Membrane Receptor Complex: TRANSFER FROM CD14 TO TLR4 AND MD-2*. J Biol Chem 276(24):21129\u201321135. https:\/\/doi.org\/10.1074\/jbc.M009164200","journal-title":"J Biol Chem"},{"issue":"11","key":"2702_CR16","doi-asserted-by":"publisher","first-page":"4825","DOI":"10.1007\/s12035-020-02066-2","volume":"57","author":"TT Oo","year":"2020","unstructured":"Oo TT, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2020) Potential Roles of Myeloid Differentiation Factor 2 on Neuroinflammation and Its Possible Interventions. Mol Neurobiol 57(11):4825\u20134844. https:\/\/doi.org\/10.1007\/s12035-020-02066-2","journal-title":"Mol Neurobiol"},{"issue":"6","key":"2702_CR17","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1038\/nm1246","volume":"11","author":"SR Krutzik","year":"2005","unstructured":"Krutzik SR, Tan B, Li H, Ochoa MT, Liu PT, Sharfstein SE, Graeber TG, Sieling PA, Liu YJ, Rea TH, Bloom BR, Modlin RL (2005) TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. Nat Med 11(6):653\u2013660. https:\/\/doi.org\/10.1038\/nm1246","journal-title":"Nat Med"},{"issue":"7","key":"2702_CR18","doi-asserted-by":"publisher","first-page":"2478","DOI":"10.1523\/jneurosci.22-07-02478.2002","volume":"22","author":"S Lehnardt","year":"2002","unstructured":"Lehnardt S, Lachance C, Patrizi S, Lefebvre S, Follett PL, Jensen FE, Rosenberg PA, Volpe JJ, Vartanian T (2002) The toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J Neurosci 22(7):2478\u20132486. https:\/\/doi.org\/10.1523\/jneurosci.22-07-02478.2002","journal-title":"J Neurosci"},{"issue":"1","key":"2702_CR19","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/jid.2012.267","volume":"133","author":"L Chen","year":"2013","unstructured":"Chen L, Guo S, Ranzer MJ, DiPietro LA (2013) Toll-Like Receptor 4 Has an Essential Role in Early Skin Wound Healing. J Invest Dermatology 133(1):258\u2013267. https:\/\/doi.org\/10.1038\/jid.2012.267","journal-title":"J Invest Dermatology"},{"issue":"14","key":"2702_CR20","doi-asserted-by":"publisher","first-page":"8514","DOI":"10.1073\/pnas.1432609100","volume":"100","author":"S Lehnardt","year":"2003","unstructured":"Lehnardt S, Massillon L, Follett P, Jensen FE, Ratan R, Rosenberg PA, Volpe JJ, Vartanian T (2003) Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway. Proc Natl Acad Sci U S A 100(14):8514\u20138519. https:\/\/doi.org\/10.1073\/pnas.1432609100","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2702_CR21","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/1742-2094-9-230","volume":"9","author":"S Leow-Dyke","year":"2012","unstructured":"Leow-Dyke S, Allen C, Denes A, Nilsson O, Maysami S, Bowie AG, Rothwell NJ, Pinteaux E (2012) Neuronal Toll-like receptor 4 signaling induces brain endothelial activation and neutrophil transmigration in vitro. J Neuroinflammation 9:230. https:\/\/doi.org\/10.1186\/1742-2094-9-230","journal-title":"J Neuroinflammation"},{"key":"2702_CR22","doi-asserted-by":"publisher","unstructured":"Yu M, Wang H, Ding A, Golenbock DT, Latz E, Czura CJ, Fenton MJ, Tracey KJ, Yang H (2006) HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock 26(2):174\u2013179. https:\/\/doi.org\/10.1097\/01.shk.0000225404.51320.82","DOI":"10.1097\/01.shk.0000225404.51320.82"},{"issue":"1","key":"2702_CR23","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1084\/jem.20141318","volume":"212","author":"H Yang","year":"2015","unstructured":"Yang H, Wang H, Ju Z, Ragab AA, Lundb\u00e4ck P, Long W, Valdes-Ferrer SI, He M, Pribis JP, Li J, Lu B, Gero D, Szabo C, Antoine DJ, Harris HE, Golenbock DT, Meng J, Roth J, Chavan SS, Andersson U, Billiar TR, Tracey KJ, Al-Abed Y (2015) MD-2 is required for disulfide HMGB1-dependent TLR4 signaling. J Exp Med 212(1):5\u201314. https:\/\/doi.org\/10.1084\/jem.20141318","journal-title":"J Exp Med"},{"issue":"5633","key":"2702_CR24","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1126\/science.1087262","volume":"301","author":"M Yamamoto","year":"2003","unstructured":"Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, Akira S (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301(5633):640\u2013643. https:\/\/doi.org\/10.1126\/science.1087262","journal-title":"Science"},{"issue":"11","key":"2702_CR25","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1038\/ni986","volume":"4","author":"M Yamamoto","year":"2003","unstructured":"Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, Takeuchi O, Takeda K, Akira S (2003) TRAM is specifically involved in the Toll-like receptor 4\u2013mediated MyD88-independent signaling pathway. Nat Immunol 4(11):1144\u20131150. https:\/\/doi.org\/10.1038\/ni986","journal-title":"Nat Immunol"},{"issue":"4","key":"2702_CR26","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/ni1569","volume":"9","author":"JC Kagan","year":"2008","unstructured":"Kagan JC, Su T, Horng T, Chow A, Akira S, Medzhitov R (2008) TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-\u03b2. Nat Immunol 9(4):361\u2013368. https:\/\/doi.org\/10.1038\/ni1569","journal-title":"Nat Immunol"},{"issue":"6","key":"2702_CR27","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1189\/jlb.1208763","volume":"85","author":"MH Laird","year":"2009","unstructured":"Laird MH, Rhee SH, Perkins DJ, Medvedev AE, Piao W, Fenton MJ, Vogel SN (2009) TLR4\/MyD88\/PI3K interactions regulate TLR4 signaling. J Leukoc Biol 85(6):966\u2013977. https:\/\/doi.org\/10.1189\/jlb.1208763","journal-title":"J Leukoc Biol"},{"key":"2702_CR28","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.neuro.2022.09.006","volume":"93","author":"TT Oo","year":"2022","unstructured":"Oo TT, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2022) Emerging roles of toll-like receptor 4 in chemotherapy-induced neurotoxicity. Neurotoxicology 93:112\u2013127. https:\/\/doi.org\/10.1016\/j.neuro.2022.09.006","journal-title":"Neurotoxicology"},{"issue":"1","key":"2702_CR29","doi-asserted-by":"publisher","first-page":"114091","DOI":"10.1016\/j.yexcr.2024.114091","volume":"439","author":"Z Feng","year":"2024","unstructured":"Feng Z, Chen G, Huang Y, Zhang K, Wu G, Xing W, Wu Y, Zhou Y, Sun C (2024) TAK-242 inhibits glioblastoma invasion, migration, and proneural\u2013mesenchymal transition by inhibiting TLR4 signaling. Exp Cell Res 439(1):114091. https:\/\/doi.org\/10.1016\/j.yexcr.2024.114091","journal-title":"Exp Cell Res"},{"issue":"4","key":"2702_CR30","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.stem.2016.12.001","volume":"20","author":"AG Alvarado","year":"2017","unstructured":"Alvarado AG, Thiagarajan PS, Mulkearns-Hubert EE, Silver DJ, Hale JS, Alban TJ, Turaga SM, Jarrar A, Reizes O, Longworth MS, Vogelbaum MA, Lathia JD (2017) Glioblastoma Cancer Stem Cells Evade Innate Immune Suppression of Self-Renewal through Reduced TLR4 Expression. Cell Stem Cell 20(4):450\u2013461e454. https:\/\/doi.org\/10.1016\/j.stem.2016.12.001","journal-title":"Cell Stem Cell"},{"issue":"6","key":"2702_CR31","doi-asserted-by":"publisher","first-page":"e0199211","DOI":"10.1371\/journal.pone.0199211","volume":"13","author":"IF Moretti","year":"2018","unstructured":"Moretti IF, Franco DG, de Almeida Galatro TF, Oba-Shinjo SM, Marie SKN (2018) Plasmatic membrane toll-like receptor expressions in human astrocytomas. PLoS ONE 13(6):e0199211. https:\/\/doi.org\/10.1371\/journal.pone.0199211","journal-title":"PLoS ONE"},{"issue":"1","key":"2702_CR32","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s00109-011-0807-6","volume":"90","author":"R Tewari","year":"2012","unstructured":"Tewari R, Choudhury SR, Ghosh S, Mehta VS, Sen E (2012) Involvement of TNF\u03b1-induced TLR4-NF-\u03baB and TLR4-HIF-1\u03b1 feed-forward loops in the regulation of inflammatory responses in glioma. J Mol Med (Berl) 90(1):67\u201380. https:\/\/doi.org\/10.1007\/s00109-011-0807-6","journal-title":"J Mol Med (Berl)"},{"issue":"8","key":"2702_CR33","doi-asserted-by":"publisher","first-page":"166155","DOI":"10.1016\/j.bbadis.2021.166155","volume":"1867","author":"LLP da Cruz","year":"2021","unstructured":"da Cruz LLP, de Souza PO, Dal Pr\u00e1 M, Falchetti M, de Abreu AM, Azambuja JH, Bertoni APS, Paz AHR, Ara\u00fajo AB, Visioli F, Fazolo T, da Silva GG, Worm PV, Wink MR, Zanotto-Filho A, Braganhol E (2021) TLR4 expression and functionality are downregulated in glioblastoma cells and in tumor-associated macrophages: A new mechanism of immune evasion? Biochim Biophys Acta Mol Basis Dis 1867(8):166155. https:\/\/doi.org\/10.1016\/j.bbadis.2021.166155","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"1","key":"2702_CR34","doi-asserted-by":"publisher","first-page":"114091","DOI":"10.1016\/j.yexcr.2024.114091","volume":"439","author":"Z Feng","year":"2024","unstructured":"Feng Z, Chen G, Huang Y, Zhang K, Wu G, Xing W, Wu Y, Zhou Y, Sun C (2024) TAK-242 inhibits glioblastoma invasion, migration, and proneural-mesenchymal transition by inhibiting TLR4 signaling. Exp Cell Res 439(1):114091. https:\/\/doi.org\/10.1016\/j.yexcr.2024.114091","journal-title":"Exp Cell Res"},{"issue":"3","key":"2702_CR35","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.cellsig.2012.12.001","volume":"25","author":"P Gupta","year":"2013","unstructured":"Gupta P, Ghosh S, Nagarajan A, Mehta VS, Sen E (2013) \u03b2-defensin-3 negatively regulates TLR4-HMGB1 axis mediated HLA-G expression in IL-1\u03b2 treated glioma cells. Cell Signal 25(3):682\u2013689. https:\/\/doi.org\/10.1016\/j.cellsig.2012.12.001","journal-title":"Cell Signal"},{"issue":"1","key":"2702_CR36","doi-asserted-by":"publisher","first-page":"6341","DOI":"10.1038\/s41598-018-24444-6","volume":"8","author":"E Ferrandez","year":"2018","unstructured":"Ferrandez E, Gutierrez O, Segundo DS, Fernandez-Luna JL (2018) NF\u03baB activation in differentiating glioblastoma stem-like cells is promoted by hyaluronic acid signaling through TLR4. Sci Rep 8(1):6341. https:\/\/doi.org\/10.1038\/s41598-018-24444-6","journal-title":"Sci Rep"},{"issue":"1","key":"2702_CR37","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1038\/s41598-020-79356-1","volume":"11","author":"IF Moretti","year":"2021","unstructured":"Moretti IF, Lerario AM, Trombetta-Lima M, Sola PR, da Silva Soares R, Oba-Shinjo SM, Marie SKN (2021) Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes. Sci Rep 11(1):1333. https:\/\/doi.org\/10.1038\/s41598-020-79356-1","journal-title":"Sci Rep"},{"issue":"1","key":"2702_CR38","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/s41419-025-08313-5","volume":"17","author":"Q Xie","year":"2025","unstructured":"Xie Q, Chen L, Huang Y, Yu Z, Zhu R, Li J, Zhao J, Song Y, Li H, Lu Y (2025) Autophagy-dependent secretion of ENO1 mediates chemoresistance of glioblastoma and tumor microenvironment remodeling. Cell Death Dis 17(1):79. https:\/\/doi.org\/10.1038\/s41419-025-08313-5","journal-title":"Cell Death Dis"},{"issue":"1","key":"2702_CR39","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s13046-017-0552-y","volume":"36","author":"S Han","year":"2017","unstructured":"Han S, Wang C, Qin X, Xia J, Wu A (2017) LPS alters the immuno-phenotype of glioma and glioma stem-like cells and induces in vivo antitumor immunity via TLR4. J Experimental Clin Cancer Res 36(1):83. https:\/\/doi.org\/10.1186\/s13046-017-0552-y","journal-title":"J Experimental Clin Cancer Res"},{"issue":"5","key":"2702_CR40","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41416-025-03094-2","volume":"133","author":"VM Lu","year":"2025","unstructured":"Lu VM, Chandar JS, Castro JR, Seetharam D, Govindarajan V, Ramsoomair CK, Desgraves JF, Hudson AJ, Shah AH (2025) Elucidating the association between TLR-4 expression and the clinical course of glioblastoma leptomeningeal disease. Br J Cancer 133(5):723\u2013731. https:\/\/doi.org\/10.1038\/s41416-025-03094-2","journal-title":"Br J Cancer"},{"key":"2702_CR41","doi-asserted-by":"publisher","first-page":"3467","DOI":"10.2147\/ott.S201732","volume":"12","author":"W Xu","year":"2019","unstructured":"Xu W, Hu GQ, Da Costa C, Tang JH, Li QR, Du L, Pan YW, Lv SQ (2019) Long noncoding RNA UBE2R2-AS1 promotes glioma cell apoptosis via targeting the miR-877-3p\/TLR4 axis. Onco Targets Ther 12:3467\u20133480. https:\/\/doi.org\/10.2147\/ott.S201732","journal-title":"Onco Targets Ther"},{"key":"2702_CR42","doi-asserted-by":"publisher","unstructured":"Moretti IF, Lerario AM, Sola PR, Macedo-da-Silva J, Baptista MDS, Palmisano G, Oba-Shinjo SM, Marie SKN (2023) GBM cells exhibit susceptibility to metformin treatment according to TLR4 pathway activation and metabolic and antioxidant status. Cancers (Basel) 15(3). https:\/\/doi.org\/10.3390\/cancers15030587","DOI":"10.3390\/cancers15030587"},{"issue":"1","key":"2702_CR43","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s40478-021-01151-4","volume":"9","author":"Y Kim","year":"2021","unstructured":"Kim Y, Varn FS, Park SH, Yoon BW, Park HR, Lee C, Verhaak RGW, Paek SH (2021) Perspective of mesenchymal transformation in glioblastoma. Acta Neuropathol Commun 9(1):50. https:\/\/doi.org\/10.1186\/s40478-021-01151-4","journal-title":"Acta Neuropathol Commun"},{"issue":"1","key":"2702_CR44","doi-asserted-by":"publisher","first-page":"24912","DOI":"10.1038\/srep24912","volume":"6","author":"J Cha","year":"2016","unstructured":"Cha J, Kang S-G, Kim P (2016) Strategies of Mesenchymal Invasion of Patient-derived Brain Tumors: Microenvironmental Adaptation. Sci Rep 6(1):24912. https:\/\/doi.org\/10.1038\/srep24912","journal-title":"Sci Rep"},{"issue":"7","key":"2702_CR45","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.7150\/thno.30578","volume":"9","author":"H Li","year":"2019","unstructured":"Li H, Li J, Zhang G, Da Q, Chen L, Yu S, Zhou Q, Weng Z, Xin Z, Shi L, Ma L, Huang A, Qi S, Lu Y (2019) HMGB1-Induced p62 Overexpression Promotes Snail-Mediated Epithelial-Mesenchymal Transition in Glioblastoma Cells via the Degradation of GSK-3\u03b2. Theranostics 9(7):1909\u20131922. https:\/\/doi.org\/10.7150\/thno.30578","journal-title":"Theranostics"},{"key":"2702_CR46","doi-asserted-by":"publisher","unstructured":"Zhang C, Hu B, Wang C, Hou S, Lin N (2025) Unveiling the novel value of TREM1 in the proneural-mesenchymal transition of glioma via tumor-associated macrophages. Front Immunol 16:1662351. https:\/\/doi.org\/10.3389\/fimmu.2025.1662351","DOI":"10.3389\/fimmu.2025.1662351"},{"issue":"12","key":"2702_CR47","doi-asserted-by":"publisher","first-page":"e0279186","DOI":"10.1371\/journal.pone.0279186","volume":"17","author":"M Fern\u00e1ndez-Gallardo","year":"2022","unstructured":"Fern\u00e1ndez-Gallardo M, Corzo-Lopez A, Mu\u00f1oz-Herrera D, Leyva-Leyva M, Gonz\u00e1lez-Ram\u00edrez R, Sandoval A, Delgado-Lezama R, Monjaraz E, Felix R (2022) Role of the Ca2\u2009+\u2009channel \u03b12\u03b4-1 auxiliary subunit in proliferation and migration of human glioblastoma cells. PLoS ONE 17(12):e0279186. https:\/\/doi.org\/10.1371\/journal.pone.0279186","journal-title":"PLoS ONE"},{"key":"2702_CR48","doi-asserted-by":"publisher","first-page":"155418","DOI":"10.1016\/j.cyto.2020.155418","volume":"140","author":"T Sheikh","year":"2021","unstructured":"Sheikh T, Sen E (2021) p53 affects epigenetic signature on SOCS1 promoter in response to TLR4 inhibition. Cytokine 140:155418. https:\/\/doi.org\/10.1016\/j.cyto.2020.155418","journal-title":"Cytokine"},{"key":"2702_CR49","doi-asserted-by":"publisher","first-page":"113756","DOI":"10.1016\/j.intimp.2024.113756","volume":"145","author":"S Aminizadeh","year":"2025","unstructured":"Aminizadeh S, Moslemizadeh AH, Sheibani S, Sedighi-Khovidak Z, Roholamini Z, Jafarinejad-Farsangi S, Kheirandish R, Sheibani V, Bashiri H (2025) Preventive effect of MitoQ supplementation and endurance training on glioblastoma and its consequences: TLR4\/CREB\/ NF-\u03ba\u03b2 \/IL-1\u03b2 pathway and behaviors. Int Immunopharmacol 145:113756. https:\/\/doi.org\/10.1016\/j.intimp.2024.113756","journal-title":"Int Immunopharmacol"},{"issue":"6","key":"2702_CR50","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/j.cell.2008.03.039","volume":"133","author":"T Kuilman","year":"2008","unstructured":"Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, Desmet CJ, Aarden LA, Mooi WJ, Peeper DS (2008) Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133(6):1019\u20131031. https:\/\/doi.org\/10.1016\/j.cell.2008.03.039","journal-title":"Cell"},{"issue":"2","key":"2702_CR51","doi-asserted-by":"publisher","first-page":"e9188","DOI":"10.1371\/journal.pone.0009188","volume":"5","author":"JP Copp\u00e9","year":"2010","unstructured":"Copp\u00e9 JP, Patil CK, Rodier F, Krtolica A, Beaus\u00e9jour CM, Parrinello S, Hodgson JG, Chin K, Desprez PY, Campisi J (2010) A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS ONE 5(2):e9188. https:\/\/doi.org\/10.1371\/journal.pone.0009188","journal-title":"PLoS ONE"},{"issue":"1","key":"2702_CR52","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/s41419-025-07915-3","volume":"16","author":"Y Liu","year":"2025","unstructured":"Liu Y, Feng Y, Cheng L, Xu Y, Wu A, Cheng P (2025) Profiling with senescence-associated secretory phenotype score identifies GDC-0879 as a small molecule sensitizing glioblastoma to anti-PD1. Cell Death Dis 16(1):602. https:\/\/doi.org\/10.1038\/s41419-025-07915-3","journal-title":"Cell Death Dis"},{"key":"2702_CR53","doi-asserted-by":"publisher","unstructured":"Tarumi W, Murai K, Nakahata Y, Masui K (2026) The paradox of senescence in glioblastoma: SASP as an emerging cancer hallmark. Cancers (Basel) 18(4). https:\/\/doi.org\/10.3390\/cancers18040550","DOI":"10.3390\/cancers18040550"},{"issue":"9","key":"2702_CR54","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1038\/nm1622","volume":"13","author":"L Apetoh","year":"2007","unstructured":"Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H, Amigorena S, Ryffel B, Barrat FJ, Saftig P, Levi F, Lidereau R, Nogues C, Mira J-P, Chompret A, Joulin V, Clavel-Chapelon F, Bourhis J, Andr\u00e9 F, Delaloge S, Tursz T, Kroemer G, Zitvogel L (2007) Toll-like receptor 4\u2013dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13(9):1050\u20131059. https:\/\/doi.org\/10.1038\/nm1622","journal-title":"Nat Med"},{"issue":"6","key":"2702_CR55","doi-asserted-by":"publisher","first-page":"eaaw0254","DOI":"10.1126\/sciadv.aaw0254","volume":"5","author":"P Hari","year":"2019","unstructured":"Hari P, Millar FR, Tarrats N, Birch J, Quintanilla A, Rink CJ, Fern\u00e1ndez-Duran I, Muir M, Finch AJ, Brunton VG, Passos JF, Morton JP, Boulter L, Acosta JC (2019) The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype. Sci Adv 5(6):eaaw0254. https:\/\/doi.org\/10.1126\/sciadv.aaw0254","journal-title":"Sci Adv"},{"key":"2702_CR56","doi-asserted-by":"publisher","first-page":"100549","DOI":"10.1016\/j.jbc.2021.100549","volume":"296","author":"MA Pibuel","year":"2021","unstructured":"Pibuel MA, Poodts D, D\u00edaz M, Hajos SE, Lompard\u00eda SL (2021) The scrambled story between hyaluronan and glioblastoma. J Biol Chem 296:100549. https:\/\/doi.org\/10.1016\/j.jbc.2021.100549","journal-title":"J Biol Chem"},{"issue":"2","key":"2702_CR57","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s10637-019-00788-2","volume":"38","author":"J Meg\u00edas","year":"2020","unstructured":"Meg\u00edas J, Mart\u00ednez A, San-Miguel T, Gil-Benso R, Mu\u00f1oz-Hidalgo L, Albert-Bellver D, Carratal\u00e1 A, Gozalbo D, L\u00f3pez-Gin\u00e9s C, Gil ML, Cerd\u00e1-Nicol\u00e1s M (2020) Pam(3)CSK(4), a TLR2 ligand, induces differentiation of glioblastoma stem cells and confers susceptibility to temozolomide. Invest New Drugs 38(2):299\u2013310. https:\/\/doi.org\/10.1007\/s10637-019-00788-2","journal-title":"Invest New Drugs"},{"key":"2702_CR58","doi-asserted-by":"publisher","unstructured":"Zarif Attalla K, Hassan DH, Teaima MH, Yousry C, El-Nabarawi MA, Said MA, Elhabal SF (2025) Enhanced intranasal delivery of atorvastatin via superparamagnetic iron-oxide-loaded nanocarriers: cytotoxicity and inflammation evaluation and in vivo, in silico, and network pharmacology study for targeting glioblastoma management. Pharmaceuticals (Basel) 18(3). https:\/\/doi.org\/10.3390\/ph18030421","DOI":"10.3390\/ph18030421"},{"issue":"9","key":"2702_CR59","doi-asserted-by":"publisher","first-page":"e29858","DOI":"10.1016\/j.heliyon.2024.e29858","volume":"10","author":"SM Emami Meybodi","year":"2024","unstructured":"Emami Meybodi SM, Moradi Moraddahande F, Dehghani Firoozabadi A (2024) Immunogenic cell death mediated TLR3\/4-activated MSCs in U87 GBM cell line. Heliyon 10(9):e29858. https:\/\/doi.org\/10.1016\/j.heliyon.2024.e29858","journal-title":"Heliyon"},{"issue":"10\u201311","key":"2702_CR60","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1007\/s00011-023-01801-4","volume":"72","author":"M Liu","year":"2023","unstructured":"Liu M, Kang W, Hu Z, Wang C, Zhang Y (2023) Targeting MyD88: Therapeutic mechanisms and potential applications of the specific inhibitor ST2825. Inflamm Res 72(10\u201311):2023\u20132036. https:\/\/doi.org\/10.1007\/s00011-023-01801-4","journal-title":"Inflamm Res"},{"issue":"1","key":"2702_CR61","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s40824-023-00391-w","volume":"27","author":"HS Kim","year":"2023","unstructured":"Kim HS, Park SC, Kim HJ, Lee DY (2023) Inhibition of DAMP actions in the tumoral microenvironment using lactoferrin-glycyrrhizin conjugate for glioblastoma therapy. Biomaterials Res 27(1):52. https:\/\/doi.org\/10.1186\/s40824-023-00391-w","journal-title":"Biomaterials Res"},{"issue":"1","key":"2702_CR62","doi-asserted-by":"publisher","first-page":"e10","DOI":"10.1371\/journal.pmed.1000010","volume":"6","author":"JF Curtin","year":"2009","unstructured":"Curtin JF, Liu N, Candolfi M, Xiong W, Assi H, Yagiz K, Edwards MR, Michelsen KS, Kroeger KM, Liu C, Muhammad AK, Clark MC, Arditi M, Comin-Anduix B, Ribas A, Lowenstein PR, Castro MG (2009) HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Med 6(1):e10. https:\/\/doi.org\/10.1371\/journal.pmed.1000010","journal-title":"PLoS Med"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-026-02702-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00109-026-02702-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-026-02702-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:05:46Z","timestamp":1784181946000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00109-026-02702-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":62,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["2702"],"URL":"https:\/\/doi.org\/10.1007\/s00109-026-02702-9","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]},"assertion":[{"value":"14 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"95"}}