title: Avitalized bacteria mediate tumor growth control via activation of innate immunity.
abstract: Acute bacterial infections have beneficial effects on tumor patients. To eliminate side effects evoked by viable microbes, we here assessed the immunotherapeutic potential of inactivated bacteria on colorectal carcinomas. Our In vitro results indicate a cell-specific direct cytotoxicity towards tumor cells presented by G1-arrest. Antitumoral activity was boosted in the presence of leukocytes. Long time stimulations revealed massive activation of NK cells even in complete autologous settings. In vivo, repetitive local treatment mediated tumor growth control. Evaluation of residual tumors identified increased infiltrates, with NK cells (CD49b(+), NKG2D(+)) being the main responding cell population. Substantial NK cell-mediated delay of tumor growth was also achieved in T-cell deficient mice xenografted with human colorectal carcinomas. Of note, local as well as systemic therapy mediated tumor growth control. These data highlight the potential of avitalized bacteria to especially activate the immune system's innate arm and they should be considered for future integrated immunotherapy.
authors.affiliation: Department of General, Vascular, Thoracic and Transplantation Surgery, Section of Molecular Oncology and Immunotherapy, University of Rostock, 18055 Rostock, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Klier
authors.forename: Claudia
authors.initials: C
authors.lastname: Maletzki
authors.forename: Nadeshda
authors.initials: N
authors.lastname: Göttmann
authors.forename: Bernd
authors.initials: B
authors.lastname: Kreikemeyer
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebacher
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D016233:Immunotherapy, Active / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D013211:Staphylococcus aureus / Q000276:immunology; D013291:Streptococcus / Q000276:immunology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology