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The Optimal Radiation Dose to Induce Robust Systemic Anti-Tumor Immunity
Version 1
: Received: 13 September 2018 / Approved: 13 September 2018 / Online: 13 September 2018 (06:33:37 CEST)
A peer-reviewed article of this Preprint also exists.
Poleszczuk, J.; Enderling, H. The Optimal Radiation Dose to Induce Robust Systemic Anti-Tumor Immunity. Int. J. Mol. Sci. 2018, 19, 3377. Poleszczuk, J.; Enderling, H. The Optimal Radiation Dose to Induce Robust Systemic Anti-Tumor Immunity. Int. J. Mol. Sci. 2018, 19, 3377.
Abstract
Synergy of radiation and immune system is currently receiving significant attention in oncology as numerous studies have shown that cancer irradiation can induce strong antitumor 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 antitumor immunity are between 10-13 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 antitumor responses.
Keywords
abscopal effect; radiotherapy; immunotherapy; mathematical model
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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