Involvement of bystander effect in suppression of the cytokine production induced by heavy-ion broad beams

Mutou-Yoshihara, Yasuko; Funayama, Tomoo; Yokota, Yuichiro; Kobayashi, Yasuhiko

doi:10.3109/09553002.2012.636138

Cited by 15 publications

(10 citation statements)

References 28 publications

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“…Irradiation of THP-1 derived macrophages with 0.5–20 Gy carbon ions (18.3 MeV/n, LET 108 keV/µm) has been shown to result in decreased TNF-α and IL-6 expression. Only extremely high doses (50 Gy) of carbon ions resulted in this study in an increased IL-6 expression (107). Irradiation of monocytes and macrophages with α-particles or accelerated carbon ions in therapeutic dose ranges (fractionated scheme) may therefore negatively modulate the immune response against tumor cells.…”

Section: Cytokines and Chemokinesmentioning

confidence: 77%

“…In coculture, U937 macrophages have been shown to secrete TNF-α and IL-1α (IL-1α not at high doses) after irradiation of NCI-H446 lung cancer cells with γ-rays ( 137 Cs Source, 8 Gy) but only TNF-α after irradiation with accelerated carbon ions (290 MeV/n, LET 13 keV/µm, 2 Gy) (99). Microbeam irradiation of 0.45% of a THP-1 derived macrophage population with 5 Gy carbon ions (18.3 MeV/n, LET 108 keV/µm) using a heavy ion microbeam resulted in significantly reduced expression of TNF-α and IL-6 (107). …”

Section: Cytokines and Chemokinesmentioning

confidence: 99%

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Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

Diegeler

Hellweg

2017

Front. Immunol.

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Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

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Section: Cytokines and Chemokinesmentioning

confidence: 77%

Section: Cytokines and Chemokinesmentioning

confidence: 99%

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

Diegeler

Hellweg

2017

Front. Immunol.

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“…Mutou-Yoshihara et al (2012) showed that suppression of cytokine production was induced in the surrounding non-irradiated cells via the bystander effect (Mutou-Yoshihara et al, 2012). Bystander responses have been measured after exposures as low as a single proton or helium ion delivered to an individual cell.…”

Section: Bystander Effectmentioning

confidence: 99%

Non-targeted effects of photon and particle irradiation and the interaction with the immune system

Schmid¹,

Multhoff²

2012

Front. Oncol.

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Ionizing irradiation is an important clinical approach to treat solid tumors. Modern radiation technologies aim to selectively kill tumor cells and protect the surrounding normal tissue. The standard paradigm for radiation effects in cellular systems involves damage of the DNA including DNA double-strand breaks, which are considered as most effective in destroying tumor cells. Due to their enhanced physical and radiobiological properties, high-linear energy transfer radiation qualities are of special interest in tumor therapy. Future radiation therapy strategies aim to utilize carbon ions to effectively treat highly aggressive tumors. More recently, evidence is emerging for non-DNA targeted effects of radiation, including mutations, chromosomal aberrations, and changes in gene expression, which can occur in cells that were not directly exposed to radiation. Radiation oncologists are only gradually beginning to appreciate the clinical relevance of radiation-induced bystander effects, genomic instability, and abscopal effects. Since these effects are sensed by the immune system, a combination of immunotherapy and irradiation presents a new therapeutic opportunity in the future.

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“…Monocites of human immune cell line THP-1 were differentiated to macrophages, and, thereafter, a 0.45% fraction of the cell population was irradiated with a carbon ion microbeam. Assays of cytokine production after irradiation revealed that the production of TNF-α and IL-6 were suppressed by the bystander effect [41].…”

Section: Programmed Matrix Irradiation Without Targeting Specific Cellsmentioning

confidence: 99%

Heavy-Ion Microbeams for Biological Science: Development of System and Utilization for Biological Experiments in QST-Takasaki

Funayama

2019

QuBS

Self Cite

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Target irradiation of biological material with a heavy-ion microbeam is a useful means to analyze the mechanisms underlying the effects of heavy-ion irradiation on cells and individuals. At QST-Takasaki, there are two heavy-ion microbeam systems, one using beam collimation and the other beam focusing. They are installed on the vertical beam lines of the azimuthally-varying-field cyclotron of the TIARA facility for analyzing heavy-ion radiation effects on biological samples. The collimating heavy-ion microbeam system is used in a wide range of biological research not only in regard to cultured cells but also small individuals, such as silkworms, nematode C. elegans, and medaka fish. The focusing microbeam system was designed and developed to perform more precise target irradiation that cannot be achieved through collimation. This review describes recent updates of the collimating heavy ion microbeam system and the research performed using it. In addition, a brief outline of the focusing microbeam system and current development status is described.

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Involvement of bystander effect in suppression of the cytokine production induced by heavy-ion broad beams

Abstract: The suppression of cytokine production arose after irradiation with heavy-ions, and may also be induced in the surrounding non-irradiated cells via the bystander effect.

Cited by 15 publications

References 28 publications

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

Non-targeted effects of photon and particle irradiation and the interaction with the immune system

Heavy-Ion Microbeams for Biological Science: Development of System and Utilization for Biological Experiments in QST-Takasaki

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