title: Bacterial immunotherapy of gastrointestinal tumors.
abstract: BACKGROUND
  Cancer immunotherapy using bacteria dates back over 150 years. The deeper understanding on how the immune system interferes with the tumor microenvironment has led to the re-emergence of bacteria or their related products in immunotherapeutic concepts. In this review, we discuss recent approaches on experimental bacteriolytic therapy, emphasizing the specific interplay between bacteria, immune cells and tumor cells to break the tumor-induced tolerance.
  
  
  RESULTS
  Experimental research during the last decades demonstrated beneficial but also adverse influence of bacteria on tumor growth. There is a strong correlation between chronic infections and tumor incidence. However, acute bacterial infections have favourable effects on tumor growth often contributing to complete remission. Tumor regression is usually attributable to both direct tumor cell killing (via apoptosis and/or necrosis, depending on the applied bacteria) and indirect immune stimulation. This includes (I) elimination of immunosuppressive immune cells (i.e. tumor-associated macrophages, myeloid-derived suppressor, and regulatory T cells), (II) suppression of Th2-directed cytokine secretion (TGFα, IL10), (III) providing a pro-inflammatory micro-milieu (tumor infiltrating neutrophils) and (IV) supporting the influx of cytotoxic T cells into tumors. This finally forces the development of an immunological memory and may provide long-term protection against cancer.
  
  
  CONCLUSIONS
  Immunotherapy using bacteria is still a double-edged sword. Experiences from the last years have substantially contributed to when bacteria and defined components thereof might be integrated into immunotherapeutic concepts. Attempts in transferring this approach into the clinics are on their way.
authors.affiliation: Department of General, Vascular, Thoracic and Transplantation Surgery, University of Rostock, Rostock, Germany. Michael.linnebacher@med.uni-rostock.de
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebacher
authors.forename: Claudia
authors.initials: C
authors.lastname: Maletzki
authors.forename: Ulrike
authors.initials: U
authors.lastname: Klier
authors.forename: Ernst
authors.initials: E
authors.lastname: Klar
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001433:Bacteriolysis / Q000276:immunology*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005770:Gastrointestinal Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000276:immunology; D008854:Microscopy, Electron; D009336:Necrosis; D014407:Tumor Cells, Cultured / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic