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Review
. 2015 Oct 8:6:505.
doi: 10.3389/fimmu.2015.00505. eCollection 2015.

Radio-Immunotherapy-Induced Immunogenic Cancer Cells as Basis for Induction of Systemic Anti-Tumor Immune Responses - Pre-Clinical Evidence and Ongoing Clinical Applications

Anja Derer  1 , Lisa Deloch  1 , Yvonne Rubner  1 , Rainer Fietkau  1 , Benjamin Frey  1 , Udo S Gaipl  1
Affiliations
Review

Radio-Immunotherapy-Induced Immunogenic Cancer Cells as Basis for Induction of Systemic Anti-Tumor Immune Responses - Pre-Clinical Evidence and Ongoing Clinical Applications

Anja Derer et al. Front Immunol. .

Abstract

Radiotherapy (RT) primarily aims to locally destroy the tumor via the induction of DNA damage in the tumor cells. However, the so-called abscopal, namely systemic and immune-mediated, effects of RT move over more and more in the focus of scientists and clinicians since combinations of local irradiation with immune therapy have been demonstrated to induce anti-tumor immunity. We here summarize changes of the phenotype and microenvironment of tumor cells after exposure to irradiation, chemotherapeutic agents, and immune modulating agents rendering the tumor more immunogenic. The impact of therapy-modified tumor cells and damage-associated molecular patterns on local and systemic control of the primary tumor, recurrent tumors, and metastases will be outlined. Finally, clinical studies affirming the bench-side findings of interactions and synergies of radiation therapy and immunotherapy will be discussed. Focus is set on combination of radio(chemo)therapy (RCT) with immune checkpoint inhibitors, growth factor inhibitors, and chimeric antigen receptor T-cell therapy. Well-deliberated combination of RCT with selected immune therapies and growth factor inhibitors bear the great potential to further improve anti-cancer therapies.

Keywords: DAMP; EGFR; PD-L1; abscopal effect; anti-tumor immunity; checkpoint inhibitors; immune therapy; radiotherapy.

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Figures

Figure 1
Figure 1
Noxious agents may induce non-immunogenic and immunogenic cell death. Stressed cells can either undergo a non-immunogenic cell death resulting in their anti-inflammatory clearance. The stress-resulting damage might, however, also foster immune reactions. Immunogenic forms of cell death, main characteristics of which are displayed in the figure, stimulate the immune system especially through the release of damage associated molecular patterns (DAMPs). Dendritic cells mature, are activated and initiate a cytotoxic T-cell response against the tumor cells.
Figure 2
Figure 2
Interactions of various co-stimulatory and inhibitory molecules regulate T-cell responses, tumor cell behavior, and vascularization. Immunotherapies with agonistic or antagonistic monoclonal antibodies have been developed to modulate these interactions by stimulating or blocking their activity. In the figure, a selection of important molecular interactions, their most relevant cellular source (not exclusive), and examples of antagonistic (red lines) or agonistic (green arrow) monoclonal antibodies as well as inhibitors are displayed. Activating receptors are depicted in green, suppressive receptors are shown in red, ligands are gray. For further information, please refer to the main text.
See this image and copyright information in PMC

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References

    1. Orth M, Lauber K, Niyazi M, Friedl AA, Li M, Maihofer C, et al. Current concepts in clinical radiation oncology. Radiat Environ Biophys (2014) 53(1):1–29.10.1007/s00411-013-0497-2 - DOI - PMC - PubMed
    1. Frey B, Gaipl US. Radio-immunotherapy: the focused beam expands. Lancet Oncol (2015) 16(7):742–3.10.1016/s1470-2045(15)00055-8 - DOI - PubMed
    1. Stewart BW, Kleihues P. International agency for research on cancer, world health organization. World Cancer Report. Lyon: International Agency for Research on Cancer; (2003).
    1. Delaney G, Jacob S, Featherstone C, Barton M. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer (2005) 104(6):1129–37.10.1002/cncr.21324 - DOI - PubMed
    1. Tian H, Gao Z, Li H, Zhang B, Wang G, Zhang Q, et al. DNA damage response – a double-edged sword in cancer prevention and cancer therapy. Cancer Lett (2015) 358(1):8–16.10.1016/j.canlet.2014.12.038 - DOI - PubMed