title: Intracerebral administration of heat-inactivated Staphylococcus epidermidis enhances oncolysis and prolongs survival in a 9L orthotopic gliosarcoma model.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Neurosurgical Oncology Laboratory, Department of General Neurosurgery, University Hospital Cologne, Cologne, Germany.
authors: Mario
authors: M
authors: Löhr
authors: Marek
authors: M
authors: Molcanyi
authors: Jörg
authors: J
authors: Poggenborg
authors: Elmar
authors: E
authors: Spuentrup
authors: Matthias
authors: M
authors: Runge
authors: Gabriele
authors: G
authors: Röhn
authors: Wolfgang
authors: W
authors: Härtig
authors: Jürgen
authors: J
authors: Hescheler
authors: Jürgen A
authors: JA
authors: Hampl
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018316:Gliosarcoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D051381:Rats; D017208:Rats, Wistar; D013212:Staphylococcus epidermidis / Q000276:immunology / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D007155:Immunologic Factors