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iScience. 2020 Mar 27;23(3):100897. doi: 10.1016/j.isci.2020.100897. Epub 2020 Feb 11.

On the Immunological Consequences of Conventionally Fractionated Radiotherapy.

Author information

1
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Rebenring 56, 38106 Braunschweig, Germany.
2
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Rebenring 56, 38106 Braunschweig, Germany; Centre for Individualised Infection Medicine (CIIM), Feodor-Lynen-Straße 15, 30625 Hannover, Germany; Institute of Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Spielmannstraße 7, 38106 Braunschweig, Germany. Electronic address: mmh@theoretical-biology.de.
3
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Rebenring 56, 38106 Braunschweig, Germany. Electronic address: haralampos.hatzikirou@theoretical-biology.de.

Abstract

Emerging evidence demonstrates that radiotherapy induces immunogenic death on tumor cells that emit immunostimulating signals resulting in tumor-specific immune responses. However, the impact of tumor features and microenvironmental factors on the efficacy of radiation-induced immunity remains to be elucidated. Herein, we use a calibrated model of tumor-effector cell interactions to investigate the potential benefits and immunological consequences of radiotherapy. Simulations analysis suggests that radiotherapy success depends on the functional tumor vascularity extent and reveals that the pre-treatment tumor size is not a consistent determinant of treatment outcomes. The one-size-fits-all approach of conventionally fractionated radiotherapy is predicted to result in some overtreated patients. In addition, model simulations also suggest that an arbitrary increase in treatment duration does not necessarily result in better tumor control. This study highlights the potential benefits of tumor-immune ecosystem profiling during treatment planning to better harness the immunogenic potential of radiotherapy.

KEYWORDS:

Bioinformatics; Cancer; Mathematical Biosciences

Conflict of interest statement

Declaration of Interests The authors declare that no conflict of interests exist.

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