title: Therapeutic Potential of Bacteria against Solid Tumors.
abstract: Intentional bacterial infections can produce efficacious antitumor responses in mice, rats, dogs, and humans. However, low overall success rates and intense side effects prevent such approaches from being employed clinically. In this work, we titered bacteria and/or the proinflammatory cytokine TNFα in a set of established murine models of cancer. To interpret the experiments conducted, we considered and calibrated a tumor-effector cell recruitment model under the influence of functional tumor-associated vasculature. In this model, bacterial infections and TNFα enhanced immune activity and altered vascularization in the tumor bed. Information to predict bacterial therapy outcomes was provided by pretreatment tumor size and the underlying immune recruitment dynamics. Notably, increasing bacterial loads did not necessarily produce better long-term tumor control, suggesting that tumor sizes affected optimal bacterial loads. Short-term treatment responses were favored by high concentrations of effector cells postinjection, such as induced by higher bacterial loads, but in the longer term did not correlate with an effective restoration of immune surveillance. Overall, our findings suggested that a combination of intermediate bacterial loads with low levels TNFα administration could enable more favorable outcomes elicited by bacterial infections in tumor-bearing subjects.Cancer Res; 77(7); 1553-63. ©2017 AACR.
authors.affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.
authors.forename: Haralampos
authors.initials: H
authors.lastname: Hatzikirou
authors.affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López Alfonso
authors.affiliation: Molecular Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Leschner
authors.affiliation: Molecular Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany.|Institute of Immunology, Medical School Hannover, Hannover, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany. michael.meyer-hermann@helmholtz-hzi.de.|Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer-Hermann
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D058491:Bacterial Load; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008962:Models, Theoretical; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D047368:Tumor Burden; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
chemical_list: D014409:Tumor Necrosis Factor-alpha