title: Induction of CD4(+) and CD8(+) anti-tumor effector T cell responses by bacteria mediated tumor therapy.
abstract: Facultative anaerobic bacteria like E. coli can colonize solid tumors often resulting in tumor growth retardation or even clearance. Little mechanistic knowledge is available for this phenomenon which is however crucial for optimization and further implementation in the clinic. Here, we show that intravenous injections with E. coli TOP10 can induce clearance of CT26 tumors in BALB/c mice. Importantly, re-challenging mice which had cleared tumors showed that clearance was due to a specific immune reaction. Accordingly, lymphopenic mice never showed tumor clearance after infection. Depletion experiments revealed that during induction phase, CD8(+) T cells are the sole effectors responsible for tumor clearance while in the memory phase CD8(+) and CD4(+) T cells were involved. This was confirmed by adoptive transfer. CD4(+) and CD8(+) T cells could reject newly set tumors while CD8(+) T cells could even reject established tumors. Detailed analysis of adoptively transferred CD4(+) T cells during tumor challenge revealed expression of granzyme B, FasL, TNF-α and IFN-γ in such T cells that might be involved in the anti-tumor activity. Our findings should pave the way for further optimization steps of this promising therapy.
authors: Department of Molecular Immunology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors: Christian
authors: C
authors: Stern
authors: Department of Molecular Immunology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors: Nadine
authors: N
authors: Kasnitz
authors: Department of Molecular Immunology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors: Dino
authors: D
authors: Kocijancic
authors: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors: Stephanie
authors: S
authors: Trittel
authors: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors: Peggy
authors: P
authors: Riese
authors: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors: Carlos A
authors: CA
authors: Guzman
authors: Department of Molecular Immunology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors: Sara
authors: S
authors: Leschner
authors: Department of Molecular Immunology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors: Siegfried
authors: S
authors: Weiss
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000382:microbiology* / Q000628:therapy*; D004926:Escherichia coli / Q000276:immunology*; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D053804:Granzymes / Q000378:metabolism; D016219:Immunotherapy, Adoptive; D007275:Injections, Intravenous; D007371:Interferon-gamma; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053804:Granzymes
keywords: CD4+; CD8+; E. coli Top10; T cells; tumor antigen presentation; tumor necrosis