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Antigen-independent immune responses after dendritic cell vaccination

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Abstract

The ability of cultured, antigen-loaded dendritic cells (DCs) to induce antigen-specific T cell immunity in vivo has previously been demonstrated and confirmed. Immune monitoring naturally focuses on immunity against vaccine antigens and may thus ignore other effects of DC vaccination. Here we therefore focused on antigen-independent responses induced by DC vaccination of renal cell carcinoma patients.

In addition to the anticipated response against the vaccine antigen KLH, vaccination with CD83+ monocyte-derived DCs resulted in a strong increase in the ex vivo proliferative and cytokine responses of PBMCs stimulated with LPS or BCG. In addition, LPS strongly enhanced the KLH-induced proliferative and cytokine response of PBMCs. Moreover, proliferative and cytokine responses of PBMCs stimulated with the homeostatic cytokines IL-7 and IL-15 were also clearly enhanced after DC vaccination. In contrast to LPS induced proliferation, which is well known to depend on monocytes, IL-7 induced proliferation was substantially enhanced after monocyte depletion indicating that monocytes limit IL-7 induced lymphocyte expansion.

Our data indicate that DC vaccination leads to an increase in the ex vivo responsiveness of patient PBMCs consistent with a DC vaccination induced enhancement of T cell memory. Our findings also suggest that incorporation of bacterial components and homeostatic cytokines into immunotherapy protocols may be useful in order to enhance the efficacy of DC vaccination and that monocytes may limit DC vaccination induced immunity.

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Acknowledgments

This work was supported by a grant awarded to Martin Thurnher from the kompetenzzentrum medizin tirol (KMT), a center of excellence. We thank Gordon Koell (KMT) and the Tilak GesmbH, the holding company of our hospital for continuous support.

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Authors and Affiliations

  1. Department of Urology, Innsbruck Medical University, 6020, Innsbruck, Austria

    Nicolai Leonhartsberger, Reinhold Ramoner, Thomas Putz, Hubert Gander, Andrea Rahm, Claudia Falkensammer, Georg Bartsch & Martin Thurnher

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  1. Nicolai Leonhartsberger
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  2. Reinhold Ramoner
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  3. Thomas Putz
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  4. Hubert Gander
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  5. Andrea Rahm
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  6. Claudia Falkensammer
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  7. Georg Bartsch
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  8. Martin Thurnher
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Correspondence to Martin Thurnher.

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Supported by a grant to Martin Thurnher from the kompetenzzentrum medizin tirol (kmt), a center of excellence.

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Leonhartsberger, N., Ramoner, R., Putz, T. et al. Antigen-independent immune responses after dendritic cell vaccination. Cancer Immunol Immunother 56, 897–903 (2007). https://doi.org/10.1007/s00262-006-0245-4

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  • DOI: https://doi.org/10.1007/s00262-006-0245-4

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