A novel experimental in vivo model of cerebral immunomodulation induced by inactivated Staphylococcus epidermidis

Löhr, Mario; Molcanyi, Marek; Stenzel, Werner; Seifert, Harald; Tzouras, Georgios; Röhn, Gabriele; Mohseni, Daud; Hampl, Jürgen A.

doi:10.1016/j.jneumeth.2011.09.016

Cited by 1 publication

(6 citation statements)

References 29 publications

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“…Their distinct and sustained recruitment is indeed most likely costimulated by tumor-associated antigens, as mere i.c. HISE application resulted in a persistent, but only scattered infiltration as demonstrated recently [19]. To activate a CD4 + response, tumor antigen epitopes must be presented concomitantly with an MHC Class II complex, e.g.…”

Section: Discussionmentioning

confidence: 82%

“…The common mechanism of action of such immunostimulatory adjuvants (ISA) like inactivated whole bacteria such as S. epidermidis [19] or Bacillus Calmette-Guérin [20], bacterial cell-wall peptides [21,22,23], or synthetic molecules like imiquimod [24,25] is the activation of Toll-like receptors, and the subsequent attraction and stimulation of antigen-presenting cells resulting in selective lysis of glioma cells.…”

Section: Discussionmentioning

confidence: 99%

“…Since we demonstrated recently that the widespread infiltration of CTLs after i.c. HISE injection reached its peak on day 4 and fell off thereafter [19], we hypothesize that only the initial steps of the cytotoxic response were triggered by HISE. The sustained trafficking of CTLs was possibly due to their specific targeting of tumor-associated antigens, probably after T-cell priming and clonal expansion in CNS-draining lymph nodes and subsequent homing back to the site of the antigenic threat in the brain [26].…”

Section: Discussionmentioning

confidence: 99%

“…administration [19]. Besides, macrophages were presumably attracted by the necrotic remnants in the center of the lesions, acting there as scavengers like in the animal cured from the gliosarcoma, where they were still detectable in the porencephalic defect.…”

Section: Discussionmentioning

confidence: 99%

“…injection of inactivated staphylococci into Wistar rats caused a rapid and sustained influx of various systemic immunocompetent cells into the CNS in a reproducible timecourse including, among others, macrophages and CD8 + cytotoxic T-lymphocytes. Moreover, the inflammation was locally restricted to the site of the deposit of the inactivated bacteria, and all experimental animals tolerated the procedure well without signs of cerebral infection [19]. …”

Section: Introductionmentioning

confidence: 99%

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Intracerebral Administration of Heat-InactivatedStaphylococcusEpidermidisEnhances Oncolysis and Prolongs Survival in a 9L Orthotopic Gliosarcoma Model

Löhr

Molcanyi

Poggenborg

et al. 2013

Cell Physiol Biochem

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Background/Aims: The association between postoperative infection and prolonged survival in high-grade glioma is still a matter of debate. Previously we demonstrated that the intracerebral (i.c.) injection of heat-inactivated staphylococcal epitopes (HISE) resulted in a well-defined infux of immunocompetent cells across the blood-brain barrier. The present study investigated the potential antitumoral effect of HISE-immunostimulation in an experimental glioma model. Methods: Wistar rats were intracerebrally implanted with 9L gliosarcoma cells (n=6), 9L cells mixed with HISE (n=12), or phosphate buffered saline (n=4). Tumor growth was measured by serial magnetic resonance imaging (MRI). After death due to the tumor burden, the brains were histopathologically assessed for inflammation and oncolysis. A toxicity assay was performed to quantify potential impairment of HISE on tumor cell growth in vitro. Results: Animals treated by HISE showed a significant increase in average survival and even complete regression of an already established mass in one case. Naïve 9L gliosarcomas failed to recruit significant numbers of systemic immune cells. In contrast, concomitant intracerebral HISE inoculation lead to a oncolysis and a distinct peri- and intratumoral infiltration of macrophages, CD8 and CD4 co-expressing T-lymphocytes in two thirds of the tumor-bearing animals. The toxicity screening showed HISE-mediated oncolysis to be ineffective ex vivo. Conclusion: This study describes a novel approach for combatting malignant glioma using inactivated staphylococci as potent immunomodulators. Our results provide an outline for investigating the strategic potential of bacteria as emerging future therapeutics.

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Section: Discussionmentioning

confidence: 82%