How Does Ionizing Irradiation Contribute to the Induction of Anti-Tumor Immunity?

Language
en
Document Type
Article
Issue Date
2012-10-10
Issue Year
2012
Authors
Rubner, Yvonne
Wunderlich, Roland
Rühle, Paul-Friedrich
Kulzer, Lorenz
Werthmöller, Nina
Frey, Benjamin
Weiss, Eva-Maria
Keilholz, Ludwig
Fietkau, Rainer
Gaipl, Udo S.
Editor
Abstract

Radiotherapy (RT) with ionizing irradiation is commonly used to locally attack tumors. It induces a stop of cancer cell proliferation and finally leads to tumor cell death. During the last years it has become more and more evident that besides a timely and locally restricted radiation-induced immune suppression, a specific immune activation against the tumor and its metastases is achievable by rendering the tumor cells visible for immune attack. The immune system is involved in tumor control and we here outline how RT induces anti-inflammation when applied in low doses and contributes in higher doses to the induction of anti-tumor immunity. We especially focus on how local irradiation induces abscopal effects. The latter are partly mediated by a systemic activation of the immune system against the individual tumor cells. Dendritic cells are the key players in the initiation and regulation of adaptive anti-tumor immune responses. They have to take up tumor antigens and consecutively present tumor peptides in the presence of appropriate co-stimulation. We review how combinations of RT with further immune stimulators such as AnnexinA5 and hyperthermia foster the dendritic cell-mediated induction of anti-tumor immune responses and present reasonable combination schemes of standard tumor therapies with immune therapies. It can be concluded that RT leads to targeted killing of the tumor cells and additionally induces non-targeted systemic immune effects. Multimodal tumor treatments should therefore tend to induce immunogenic tumor cell death forms within a tumor microenvironment that stimulates immune cells.

Journal Title
Frontiers in Oncology
Citation
Frontiers in Oncology 2.75 (2012): 10.10.2012 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404483/>
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