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Abstract
During the response to ionizing radiation, several mechanisms interact, including direct damage of DNA, vascular endothelial cell apoptosis, immune cell death, and the development of non-target effects. The contribution of each of these mechanisms to the overall biological response varies depending on the radiation regimen, and primary on the dose per fraction. At high-dose irradiation and significant doses per fraction, indirect (vascular, immune, and non-targeted) tumor cell death becomes of primary importance. Non-targeted radiobiological effects, observed in cells and tissues not directly exposed to ionizing radiation, are insufficiently studied, exhibit poor predictability, and have garnered growing interest among researchers. These effects contribute to the evolving concept of modern radiobiology and can be comprehensively studied through the interrelation of three main models: linear-quadratic, vascular, and immune. The non-targeted abscopal effect, including its specific manifestation, known as the "bystander effect," involve the transmission of radiation signals (primarily apoptosis) from irradiated to non-irradiated cells via intercellular contacts and mediator secretion. This occurs due to intense immune system stimulation caused by massive expression of tumor antigens. Non-targeted effects can have both positive (radioprotective) and more commonly negative (radiosensitizing) influences. The low frequency of abscopal effects is partly attributed to the suppressive influence of the tumor microenvironment. Understanding the mechanisms behind these radiobiological phenomena facilitates exploring and implementing combined approaches involving radiation, immunotherapy, and chemotherapy to achieve synergistic effects.
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