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[Effect of low dose heavy ion irradiation on subset percentage and cytokines expression of peripheral blood lymphocytes in patients with pancreatic cancer].

OBJECTIVE
The aim of this study was to examine the effect of low dose heavy ion irradiation on the subset percentage and expression of cytokines of peripheral blood lymphocytes(PBL) in patients with pancreatic cancer.


METHODS
PBL from 21 patients with pancreatic cancer were divided into three groups: sham, X-ray and ¹²C⁶⁺ irradiation groups, and the cell responses were measured at 24 hours after radiation exposure. The percentages of T and NK cell subsets were detected by flow cytometry. The mRNA expression of interleukin (IL)-2, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were examined by real-time quantitative RT-PCR (qRT-PCR). The cytokine protein levels in supernatant of cultured cells were assayed by enzyme-linked immunosorbent assays (ELISA).


RESULTS
The percentage of T lymphocyte subsets was significantly increased at 24 hours after exposure to low dose radiation, and the effect was more pronounced in the group receiving 0.05 Gy ¹²C⁶⁺ ion irradiation than that in the group receiving X-ray irradiation [CD3⁺ T cells: (67.15 ± 4.36)% vs. (60.81 ± 8.35)%; CD3⁺ CD4⁺ T cells: (19.02 ± 2.35)% vs. (17.21 ± 2.86)%; CD3⁺ CD8⁺ T cells: (46.59 ± 6.07)% vs. (41.18 ± 6.35)%. (P < 0.05 for all)]. However, there were no significant changes in the CD3⁺ CD4⁺/CD3⁺ CD8⁺ ratio (0.67 for sham, 0.65 for X-ray, and 0.68 for ¹²C⁶⁺ groups) and percentage of NK cell subsets (P > 0.05 for all). Expression levels of IFN-γ mRNA (cycle threshold/CT value was 23.35 ± 3.16 for ¹²C⁶⁺, CT value was 27.25 ± 2.15 for X-ray) and IL-2 (CT value was 24.19 ± 3.56 for ¹²C⁶⁺, CT value was 27.85 ± 4.08 for X-ray) in PBL, and their protein levels in the supernatant were significantly increased at 24 hours after exposure to the low dose radiation (P < 0.05). The effects were more pronounced in the group receiving 0.05 Gy ¹²C⁶⁺ ion irradiation than that in the group receiving X-ray irradiation. However, there was no significant change in the TNF-α production of PBL.


CONCLUSIONS
Low dose irradiation may alleviate the immune suppression caused by tumor burden and that the effect is more pronounced for 0.05 Gy high linear energy transfer (LET) ¹²C⁶⁺ irradiation. The percentage of T cell subsets and cytokines production could be used as sensitive indicators of acute response to low dose irradiation.