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Anticancer Res. 2018 Feb;38(2):655-663.

Natural Killer Cell Viability After Hyperthermia Alone or Combined with Radiotherapy with or without Cytokines.

Author information

1
Department of Oncology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland tenho@hietanen.net.
2
Department of Oncology, Tampere University Hospital, Tampere, Finland.
3
Department of Medical Physics, Tampere University Hospital, Tampere, Finland.
4
Department of Oncology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

Abstract

BACKGROUND:

The effects of hyperthermia and irradiation, alone and in combination, on natural killer (NK) cell viability were investigated in vitro. The roles of interleukin-2 (IL-2) and interferon (IFN) α, β and γ in rescuing NK cells from hyperthermia and irradiation were studied.

MATERIALS AND METHODS:

Non-selected NK cells were used as effector cells and K-562 cells as target cells. NK and K-562 cells were treated at 37 to 45°C for 0 to 180 min. The cells were irradiated at room temperature using single doses from 0 to 60 Gy. Recombinant IL-2 at 100 to 450 U/ml and recombinant IFNα, β and γ at 1,000 U/ml were used for different periods of time. NK cell viability was measured by intracellular adenosine tri-, and diphosphate (ATP, ADP) levels via luminometer, trypan blue exclusion and propidium iodide (PI) staining. Binding capacity of NK effector cells to target K-562 cells was also microscopically assessed.

RESULTS:

Thermal treatments between 37 and 41°C did not significantly affect the ATP levels of NK cells. Between 41°C and 42°C, ATP levels significantly decreased, whilst there was an insignificant reduction up to 45°C. At 42°C or higher, no recovery was detectable. At 42°C, the ATP level of NK cells rescued by IL-2 were significantly higher than those of controls at 37°C. IFNα, β and γ had no significant effects. A combination of heating at 42°C and irradiation at 20 Gy significantly reduced the ATP levels (p<0.001) more than heating and irradiation alone. At 42°C, IL-2 abolished the reduction of ATP levels by heating and irradiation. This effect was dependent on heating time and irradiation dose. The ATP/ADP ratio did not significantly change when NK cells were heated for different times at 42°C. Thermal treatment of target K-562 cells at temperatures from 37 to 45°C reduced the number of NK cells binding K-652 cells.

CONCLUSION:

In vitro, NK cell viability was strongly reduced between 41°C and 42°C. At 42°C, the combination of irradiation and thermal treatment reduced the ATP levels in NK cells. However, IL-2 restored cell viability depending on thermal and radiation doses.

KEYWORDS:

ADP; ATP; IFN; IL-2; Natural killer (NK) cells; hyperthermia; irradiation; recovery; viability

PMID:
29374687
DOI:
10.21873/anticanres.12269
[Indexed for MEDLINE]

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