High-grade gliomas are primary brain tumors with poor prognosis, despite surgical treatment followed by radiotherapy and concomitant chemotherapy. We present two cases of long-term survival in patients treated for high-grade glioma and concomitant prolonged bacterial wound infection. The first patient treated for glioblastoma IDH-wildtype had been without disease progression for 61 months from the first resected recurrence. Despite incomplete chemotherapy-induced myelosuppression in the second patient with anaplastic astrocytoma IDH-mutant, she died without disease relapse after 14 years from the diagnosis due to other comorbidities. We assume that the documented prolonged survival could be related to the bacterial infection.

1st Department of Pathology St Anne's University Hospital Brno Brno Czechia

1st Department of Pathology St Anne's University Hospital Brno Faculty of Medicine Masaryk University Brno Czechia

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Faculty of Medicine Masaryk University Brno Czechia

Department of Neurosurgery St Anne's University Hospital Brno Brno Czechia

Department of Neurosurgery St Anne's University Hospital Brno Faculty of Medicine Masaryk University Brno Czechia

Department of Radiation Oncology Masaryk Memorial Cancer Institute Faculty of Medicine Masaryk University Brno Czechia

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Lakomy R, Kazda T, Selingerova I, Poprach A, Pospisil P, Belanova R, et al. . Real-world evidence in glioblastoma: Stupp’s regimen after a decade. Front Oncol (2020) 10:840. doi: 10.3389/fonc.2020.00840 PubMed DOI PMC

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. . The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol (2016) 131:803–20. doi: 10.1007/s00401-016-1545-1 PubMed DOI

Razavi S-M, Lee KE, Jin BE, Aujla PS, Gholamin S, Li G. Immune evasion strategies of glioblastoma. Front Surg (2016) 3:11. doi: 10.3389/fsurg.2016.00011 PubMed DOI PMC

Tivnan A, Heilinger T, Lavelle EC, Prehn JHM. Advances in immunotherapy for the treatment of glioblastoma. J Neurooncol (2017) 131:1–9. doi: 10.1007/s11060-016-2299-2 PubMed DOI PMC

Wei MQ, Mengesha A, Good D, Anné J. Bacterial targeted tumour therapy-dawn of a new era. Cancer Lett (2008) 259:16–27. doi: 10.1016/j.canlet.2007.10.034 PubMed DOI

Kazim SF, Martinez E, Hough TJ, Spangler BQ, Bowers CA, Chohan MO. The survival benefit of postoperative bacterial infections in patients with glioblastoma multiforme: Myth or reality? Front Neurol (2021) 12:615593. doi: 10.3389/fneur.2021.615593 PubMed DOI PMC

Bohman L-E, Gallardo J, Hankinson TC, Waziri AE, Mandigo CE, McKhann GM, et al. . The survival impact of postoperative infection in patients with glioblastoma multiforme. Neurosurgery (2009) 64:828–34. doi: 10.1227/01.NEU.0000343525.89321.C5 PubMed DOI

Chen Y-R, Ugiliweneza B, Burton E, Woo SY, Boakye M, Skirboll S. The effect of postoperative infection on survival in patients with glioblastoma. J Neurosurg (2017) 127:807–11. doi: 10.3171/2016.8.JNS16836 PubMed DOI

Alexiou GA, Kallinteri A, Michos E, Zagorianakou P, Priavali E, Pachatouridis D, et al. . The influence of postoperative infection in survival of patients with high-grade gliomas. Neuroimmunol Neuroinflamm (2015) 2:18–20. doi: 10.4103/2347-8659.149418 DOI

De Bonis P, Albanese A, Lofrese G, de Waure C, Mangiola A, Pettorini BL, et al. . Postoperative infection may influence survival in patients with glioblastoma: simply a myth? Neurosurgery (2011) 69:864–8. doi: 10.1227/NEU.0b013e318222adfa PubMed DOI

Walker DG, Pamphlett R. Prolonged survival and pulmonary metastasis after local cure of glioblastoma multiforme. J Clin Neurosci (1999) 6:67–8. doi: 10.1016/s0967-5868(99)90611-2 PubMed DOI

Chicoine MR, Won EK, Zahner MC. Intratumoral injection of lipopolysaccharide causes regression of subcutaneously implanted mouse glioblastoma multiforme. Neurosurgery (2001) 48:607–14. doi: 10.1097/00006123-200103000-00032 PubMed DOI

Chicoine MR, Zahner M, Won EK, Kalra RR, Kitamura T, Perry A, et al. . The in vivo antitumoral effects of lipopolysaccharide against glioblastoma multiforme are mediated in part by toll-like receptor 4. Neurosurgery (2007) 60:372–80. doi: 10.1227/01.NEU.0000249280.61761.2E PubMed DOI

Won EK, Zahner MC, Grant EA, Gore P, Chicoine MR. Analysis of the antitumoral mechanisms of lipopolysaccharide against glioblastoma multiforme. Anticancer Drugs (2003) 14:457–66. doi: 10.1097/00001813-200307000-00012 PubMed DOI

Dickinson H, Carico C, Nuño M, Mukherjee D, Ortega A, Black KL, et al. . Unplanned readmissions and survival following brain tumor surgery. J Neurosurg (2015) 122:61–8. doi: 10.3171/2014.8.JNS1498 PubMed DOI

van Solinge TS, Nieland L, Chiocca EA, Broekman MLD. Advances in local therapy for glioblastoma — taking the fight to the tumour. Nat Rev Neurol (2022) 18:221–36. doi: 10.1038/s41582-022-00621-0 PubMed DOI PMC

Ohkuri T, Ghosh A, Kosaka A, Zhu J, Ikeura M, David M, et al. . STING contributes to antiglioma immunity via triggering type I IFN signals in the tumor microenvironment. Cancer Immunol Res (2014) 2:1199–208. doi: 10.1158/2326-6066.CIR-14-0099 PubMed DOI PMC

Bowles AP, Perkins E. Long-term remission of malignant brain tumors after intracranial infection: a report of four cases. Neurosurgery (1999) 44:636–42. doi: 10.1097/00006123-199903000-00110 PubMed DOI

Yamamura M, Amano Y, Sakagami H, Yamanaka Y, Nishimoto Y, Yoshida H, et al. . Calcium mobilization during nicotine-induced cell death in human glioma and glioblastoma cell lines. Anticancer Res (1998) 18:2499–502. PubMed

Li W, Graeber MB. The molecular profile of microglia under the influence of glioma. Neuro-Oncology (2012) 14:958–78. doi: 10.1093/neuonc/nos116 PubMed DOI PMC

Akasaki Y, Liu G, Chung NHC, Ehtesham M, Black KL, Yu JS. Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-Overexpressing glioma. J Immunol (2004) 173:4352–9. doi: 10.4049/jimmunol.173.7.4352 PubMed DOI

Bloch O, Crane CA, Kaur R, Safaee M, Rutkowski MJ, Parsa AT. Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res (2013) 19:3165–75. doi: 10.1158/1078-0432.CCR-12-3314 PubMed DOI PMC

Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev (2009) 22:240–73. doi: 10.1128/CMR.00046-08 PubMed DOI PMC

Avril T, Vauleon E, Tanguy-Royer S, Mosser J, Quillien V. Mechanisms of immunomodulation in human glioblastoma. Immunotherapy (2011) 3:42–4. doi: 10.2217/imt.11.39 PubMed DOI

Naganuma H, Sasaki A, Satoh E, Nagasaka M, Isoe S, Nakano S, et al. . Long-term survival in a young patient with anaplastic glioma. Brain Tumor Pathol (1997) 14:71–4. doi: 10.1007/BF02478872 PubMed DOI

Chen J, Zhan Y, Wang W, Jiang S, Li X. The engineered salmonella typhimurium inhibits tumorigenesis in advanced glioma. OTT (2015) 8:2555–63. doi: 10.2147/OTT.S86899 PubMed DOI PMC

Löhr M, Molcanyi M, Poggenborg J, Spuentrup E, Runge M, Röhn G, et al. . Intracerebral administration of heat-inactivated staphylococcus epidermidis enhances oncolysis and prolongs survival in a 9L orthotopic gliosarcoma model. Cell Physiol Biochem (2013) 31:614–24. doi: 10.1159/000350081 PubMed DOI

Salle H, Deluche E, Couvé-Deacon E, Beaujeux A-C, Pallud J, Roux A, et al. . Surgical site infections after glioblastoma surgery: results of a multicentric retrospective study. Infection (2021) 49:267–75. doi: 10.1007/s15010-020-01534-0 PubMed DOI

Zhang B, Zhang J, Fang S, Zhang M, Liu S, Tian Y, et al. . Inflammatory activation of microglia by staphylococcus aureus caused phenotypic alterations and affected glioblastoma growth. Cell Biochem Funct (2019) 37:331–9. doi: 10.1002/cbf.3396 PubMed DOI

Han S, Wang C, Qin X, Xia J, Wu A. LPS alters the immuno-phenotype of glioma and glioma stem-like cells and induces in vivo anti-tumor immunity via TLR4. J Exp Clin Cancer Res (2017) 36:83. doi: 10.1186/s13046-017-0552-y PubMed DOI PMC

Akbari A, Farahnejad Z, Akhtari J, Abastabar M, Mobini GR, Mehbod ASA. Staphylococcus aureus enterotoxin b down-regulates the expression of transforming growth factor-beta (TGF-β) signaling transducers in human glioblastoma. Jundishapur J Microbiol (2016) 9:e27297. doi: 10.5812/jjm.27297 PubMed DOI PMC

Fuller CL, Braciale VL. Selective induction of CD8+ cytotoxic T lymphocyte effector function by staphylococcus enterotoxin b. J Immunol (1998) 161:5179–86. PubMed

Lamb R, Ozsvari B, Lisanti CL, Tanowitz HB, Howell A, Martinez-Outschoorn UE, et al. . Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease. Oncotarget (2015) 6:4569–84. doi: 10.18632/oncotarget.3174 PubMed DOI PMC

McGranahan T, Li G, Nagpal S. History and current state of immunotherapy in glioma and brain metastasis. Ther Adv Med Oncol (2017) 9:347–68. doi: 10.1177/1758834017693750 PubMed DOI PMC

Di Tomaso T, Mazzoleni S, Wang E, Sovena G, Clavenna D, Franzin A, et al. . Immunobiological characterization of cancer stem cells isolated from glioblastoma patients. Clin Cancer Res (2010) 16:800–13. doi: 10.1158/1078-0432.CCR-09-2730 PubMed DOI PMC

Hegi ME, Diserens A-C, Gorlia T, Hamou M-F, de Tribolet N, Weller M, et al. . MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med (2005) 352:997–1003. doi: 10.1056/NEJMoa043331 PubMed DOI