Clinically Relevant Radiation Exposure Differentially Impacts Forms of Cell Death in Human Cells of the Innate and Adaptive Immune System

Abstract

In cancer treatments, especially high-dose radiotherapy (HDRT) is applied. Patients suffering from chronic inflammatory diseases benefit from low-dose radiation therapy (LDRT), but exposure to very low radiation doses can still steadily increase for diagnostic purposes. Yet, little is known about how radiation impacts on forms of cell death in human immune cells. In this study, the radiosensitivity of human immune cells of the peripheral blood was examined in a dose range from 0.01 to 60 Gy with regard to induction of apoptosis, primary necrosis, and secondary necrosis. Results showed that immune cells differed in their radiosensitivity, with monocytes being the most radioresistant. T cells mainly died by necrosis and were moderately radiosensitive. This was followed by B and natural killer (NK) cells, which died mainly by apoptosis. X-radiation had no impact on cell death in immune cells at very low doses (≤0.1 Gy). Radiation doses of LDRT (0.3–0.7 Gy) impacted on the more radiosensitive NK and B cells, which might contribute to attenuation of inflammation. Even single doses applied during RT of tumors did not erase the immune cells completely. These in vitro studies can be considered as the basis to optimize individual radiation therapy schemes in multimodal settings and to define suited time points for further inclusion of immunotherapies.

The interplay between cancer associated fibroblasts and immune cells in the context of radiation therapy

“…As the primary cytotoxic presence of the innate immune system and the first line of defense against tumor cells, NK cells are exceedingly important to the antitumor response 132 . However, NK cells have been shown to be more radiosensitive to high‐dose radiation than T and B lymphocytes 133 . This effect results in decreased activation of NK cells after RT and a reduced NK‐mediated tumor killing presence 134 .…”

Hematological Indexes Can Be Used to Predict the Incidence of Hypothyroidism in Nasopharyngeal Carcinoma Patients after Radiotherapy

“…Recently, a large number of studies have reported that the immune system plays a key role in radiation response [7,8], which is divided into adaptive and innate immunity. Adaptive immunity consists primarily of B and T lymphocytes.…”

Low-Level Ionizing Radiation Induces Selective Killing of HIV-1-Infected Cells with Reversal of Cytokine Induction Using mTOR Inhibitors

“…Considering the advances in RT technology, the use of IR has the potential to serve more effectively as an LRA in animal and clinical studies. Despite these advances, high radiation doses may induce multiple negative effects, such as killing of normal tissues via production of ROS and induction of double-strand DNA breaks, changes in the expression of inflammatory cytokines, chemokines, and fibrotic cytokines that result in altered cell-cell interactions and acute and chronic inflammation [166,167], the proposed treatment scheme utilizes an IR dose (0.5 Gy) that is lower than those used in cancer radiotherapy and induces minimal side effects [168,169]. Therefore, future experiments could focus on developing a therapeutic strategy for IR that, for instance, uses either low total body irradiation doses or higher local doses for strategically targeted HIV-1 reservoirs.…”