| Objective:Radiotherapy is one of the most important methods for the treatment of thoracic malignant tumors.The lung tissue is highly sensitive to the radiation,so it is easy to be injured by the radiation and lead to radiation pneumonitis.In the early stage,our research team constructed the rat model of radiation pneumonitis,indicating that the occurrence and development of radiation pneumonitis are closely related to Th17/Treg mediated immune imbalance,but the specific mechanism was not known.It has been shown that JAK/STAT signaling pathway is involved in the differentiation of T lymphocyte and the development of many inflammatory diseases.However,the mechanism of STAT3,a downstream signal molecule of JAK,in Th17/Treg imbalance in radiation pneumonitis has not been clearly elucidated.The aim of this study was to investigate the role of JAK/STAT3 signaling pathway in Th17/Treg cell-mediated immunity imbalance in patients with radiation pneumonitis.Methods:1.Patients with esophageal squamous cell carcinoma who received radiotherapy for primary lesion or mediastinal metastatic lymph node from January 2022 to December 2022 were selected in the People’s Hospital of Jiangsu University.Peripheral blood was collected at the beginning of radiotherapy,at the 2nd,4th,6th and 4th weeks after radiotherapy.2.The patients were divided into two groups according to whether they had radiation pneumonitis or not: radiation pneumonitis group and control group(non-radiation pneumonitis group).The percentage of Th17 cells,the percentage of Treg cells and the relative concentration of pSTAT3 were measured by Flow cytometry,the imbalance of Th17/Treg and the correlation between the expression of pSTAT3 and the ratio of Th17 cells,Treg cells and Th17/Treg were analyzed.3.Peripheral blood samples were collected from patients with radiation pneumonitis at the time of diagnosis and a week after glucocorticoid treatment.The expression of pSTAT3 was detected by Flow cytometry,the sensitivity of corticosteroid therapy for radiation pneumonitis was evaluated by chest CT,and the changes of pSTAT3 concentration after treatment were compared between the two groups.The purpose of this study was to determine whether the changes of pSTAT3 could predict the sensitivity of corticosteroid therapy in radiation pneumonitis.Results:1.The number and proportion of Treg and Th17 cells in peripheral blood PBMC:(1)The percentage of Treg cells in peripheral blood of patients with radiation pneumonitis was not significantly different from that of patients without radiation pneumonitis at the beginning of radiotherapy and at the 2nd and 4th weeks of radiotherapy,there was a significant difference between the radiation pneumonitis group and the control group(P = 0.010 < 0.05),the difference was more significant(P = 0.001 < 0.01);(2)The percentage of Th17 cells in the patients with radiation pneumonitis was higher than that in the patients without radiation pneumonitis(P = 0.023 < 0.05),the ratio of Th17 cells in peripheral blood was significantly different between the two groups,and the level of Th17 cells was significantly increased in the radiation pneumonia group(P < 0.05);(3)There were significant differences in Th17/Treg ratio between the two groups at the 6th week after radiotherapy and at the end of radiotherapy(P <0.05).This suggests that the development of radiation pneumonitis is associated with Th17/Treg-mediated immune imbalance in patients with esophageal cancer.2.The expression level of pSTAT3: in the patients with radiation pneumonia,the level of pSTAT3 began to increase from the 4th week of radiotherapy,and had statistical significance(P< 0.05),this was consistent with an increase in the Th17 ratio at week 4 of radiotherapy.3.Correlation Analysis: at the 6th week of radiotherapy,the expression level of pSTAT3 was positively correlated with the ratio of Th17 cells and the ratio of Th17/Treg(r = 0.654,P <0.01;r = 0.629,P < 0.05),although there was an inverse correlation between the expression level of pSTAT3 and the proportion of Treg cells,the expression level of pSTAT3 was not statistically significant(P > 0.05),there was a negative correlation between the expression of pSTAT3 and the proportion of Treg cells(r =-0.632,P < 0.05).There was a positive correlation between the expression of pSTAT3 and the proportion of Th17 cells and the ratio of Th17/Treg(r = 0.789,P < 0.01;r = 0.719,P < 0.01).4.The change of pSTAT3level predicts the sensitivity of corticosteroid therapy: no statistical analysis was performed because of the small sample size,but we still found a trend in a small number of cases,that is,in the group of patients who were diagnosed with radiation pneumonitis and were treated with corticosteroid,in patients with steroid sensitivity,the decrease in pSTAT3 level was less significant.Conclusion:The number of Th17 cells increased and the number of Treg cells decreased,and the concentration of pSTAT3 increased during the formation of radiation pneumonitis,there is a Th17/Treg imbalance at the cellular level and this imbalance is associated with the level of pSTAT3 concentration in the JAK/STAT3 signaling pathway. |
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