Next Article in Journal
Non-Coding Micro RNAs and Hypoxia-Inducible Factors Are Selenium Targets for Development of a Mechanism-Based Combination Strategy in Clear-Cell Renal Cell Carcinoma—Bench-to-Bedside Therapy
Next Article in Special Issue
Clinically Relevant Radiation Exposure Differentially Impacts Forms of Cell Death in Human Cells of the Innate and Adaptive Immune System
Previous Article in Journal
Effects of an Interchain Disulfide Bond on Tropomyosin Structure: A Molecular Dynamics Study
Previous Article in Special Issue
Stereotactic Radiosurgery and Immune Checkpoint Inhibitors in the Management of Brain Metastases
Open AccessArticle

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

Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Ks. Trojdena 4, 02-109 Warsaw, Poland
Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3377;
Received: 13 September 2018 / Revised: 8 October 2018 / Accepted: 23 October 2018 / Published: 29 October 2018
(This article belongs to the Special Issue Partnership of Radiotherapy and Immunotherapy)
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. View Full-Text
Keywords: abscopal effect; radiotherapy; immunotherapy; mathematical model abscopal effect; radiotherapy; immunotherapy; mathematical model
Show Figures

Figure 1

MDPI and ACS Style

Poleszczuk, J.; Enderling, H. The Optimal Radiation Dose to Induce Robust Systemic Anti-Tumor Immunity. Int. J. Mol. Sci. 2018, 19, 3377.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Search more from Scilit
Back to TopTop