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Int J Mol Sci. 2018 Oct 29;19(11). pii: E3377. doi: 10.3390/ijms19113377.

The Optimal Radiation Dose to Induce Robust Systemic Anti-Tumor Immunity.

Author information

1
Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Ks. Trojdena 4, 02-109 Warsaw, Poland. jpoleszczuk@ibib.waw.pl.
2
Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. heiko.enderling@moffitt.org.
3
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. heiko.enderling@moffitt.org.

Abstract

The synergy of radiation and the immune system is currently receiving significant attention in oncology as numerous studies have shown that cancer irradiation can induce strong anti-tumor immune responses. It remains unclear, however, what are the best radiation fractionation protocols to maximize the therapeutic benefits of this synergy. Here, we present a novel mathematical model that can be used to predict and dissect the complexity of the immune-mediated response at multiple tumor sites after applying focal irradiation and systemic immunotherapy. We successfully calibrate the proposed framework with published experimental data, in which two tumors were grown in mice at two spatially-separated sites from which only one was irradiated using various radiation fractionation protocols with and without concurrent systemic immunotherapy. The proposed model is calibrated to fit the temporal dynamics of tumor volume at both sites and can predict changes in immune infiltration in the non-irradiated tumors. The model was then used to investigate additional radiation fractionation protocols. Model simulations suggest that the optimal radiation doses per fraction to maximize anti-tumor immunity are between 10 and 13 Gy, at least for the experimental setting used for model calibration. This work provides the framework for evaluating radiation fractionation protocols for radiation-induced immune-mediated systemic anti-tumor responses.

KEYWORDS:

abscopal effect; immunotherapy; mathematical model; radiotherapy

PMID:
30380596
PMCID:
PMC6275030
DOI:
10.3390/ijms19113377
[Indexed for MEDLINE]
Free PMC Article

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