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    Induction of CD4(+) and CD8(+) anti-tumor effector T cell responses by bacteria mediated tumor therapy.

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    Authors
    Stern, Christian
    Kasnitz, Nadine
    Kocijancic, Dino
    Trittel, Stephanie
    Riese, Peggy cc
    Guzman, Carlos A
    Leschner, Sara
    Weiss, Siegfried cc
    Issue Date
    2015-10-15
    
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    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.
    Affiliation
    Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
    URI
    http://hdl.handle.net/10033/621431
    DOI
    10.1002/ijc.29567
    PubMed ID
    25868911
    Additional Links
    https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.29567
    Type
    Article
    ISSN
    1097-0215
    ae974a485f413a2113503eed53cd6c53
    10.1002/ijc.29567
    Scopus Count
    Collections
    publications of the research group vaccinology and applied microbiology (VAC)
    publications of the research group molecular Immunology (MOLI)

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