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Antitumor immune responses induced by ionizing irradiation and further immune stimulation

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

The therapy of cancer emerged as multimodal treatment strategy. The major mode of action of locally applied radiotherapy (RT) is the induction of DNA damage that triggers a network of events that finally leads to tumor cell cycle arrest and cell death. Along with this, RT modifies the phenotype of the tumor cells and their microenvironment. Either may contribute to the induction of specific and systemic antitumor immune responses. The latter are boosted when additional immune therapy (IT) is applied at distinct time points during RT. We will focus on therapy-induced necrotic tumor cell death that is immunogenic due to the release of damage-associated molecular patterns. Immune-mediated distant bystander (abscopal) effects of RT when combined with dendritic cell-based IT and the role of fractionation of radiation in the induction of immunogenic tumor cell death will be discussed. Autologous whole-tumor-cell-based vaccines generated by high hydrostatic pressure technology will be introduced and the influence of cytokines and the immune modulator AnnexinA5 on the ex vivo generated or in situ therapy-induced vaccine efficacy will be outlined. RT should be regarded as immune adjuvant for metastatic disease and as a tool for the generation of an in situ vaccine when applied at distinct fractionation doses or especially in combination with IT to generate immune memory against the tumor. To identify the most beneficial combination and chronology of RT with IT is presumably one of the biggest challenges of innovative tumor research and therapies.

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Acknowledgments

This work was supported by the German Research Foundation (DFG -Graduiertenkolleg 1660: Key signals of the adaptive immune response and GA 1507/1-1), the German Federal Ministry of Education and Research (BMBF; m4 Cluster, 16EX1021R and GREWIS, 02NUK017G), and the European Commissions (DoReMi, European Atomic Energy Community’s Seventh Framework Programme (FP7/2007-2011) under Grant Agreement No. 249689).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstr. 27, 91054, Erlangen, Germany

    Benjamin Frey, Yvonne Rubner, Lorenz Kulzer, Nina Werthmöller, Eva-Maria Weiss, Rainer Fietkau & Udo S. Gaipl

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  1. Benjamin Frey
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  2. Yvonne Rubner
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  3. Lorenz Kulzer
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  4. Nina Werthmöller
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  7. Udo S. Gaipl
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Correspondence to Udo S. Gaipl.

Additional information

This paper is a Focussed Research Review based on a presentation given at the Third International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2013), held in Krakow, Poland, 22nd–25th April 2013. It is part of a CII series of Focussed Research Reviews and meeting report.

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Frey, B., Rubner, Y., Kulzer, L. et al. Antitumor immune responses induced by ionizing irradiation and further immune stimulation. Cancer Immunol Immunother 63, 29–36 (2014). https://doi.org/10.1007/s00262-013-1474-y

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