The effects of stereotactic body radiotherapy on peripheral natural killer and CD3~+CD56~+ NKT-like cells in patients with hepatocellular carcinoma

Background: Both natural killer(NK) and CD3+CD56+ natural killer T(NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy(SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma(HCC), and to identify possible surface markers on these cells that correlate with the prognosis. Methods: Twenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γand TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis. Results: The peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+ NK cells before SBRT and higher percentage of CD158b + NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3+CD56+ NKT-like cells was associated with a higher overall survival rate in HCC patients. Conclusions: SBRT has an apparent effect on both peripheral NK and CD3+ CD56+ NKT-like cells. Lower percentage of NKp30 + NK cells before SBRT and higher percentage of CD158b + NK cells after SBRT are correlated with poor patients' PFS. Higher percentage of CD3+ CD56+ NKT-like cells is associated with higher OS in HCC patients.

Jinbei Oral Liquid ameliorates bleomycin-induced idiopathic pulmonary fibrosis in rats via reversion of Th1/Th2 shift

Objective:Idiopathic pulmonary fibrosis(IPF)is a progressive and lethal interstitial lung disease with high mortality.The pivotal role of Th1/Th2 immunological balance in the development and progression of IPF has been demonstrated previously.This study aimed to evaluate the effect of Jinbei Oral Liquid(JBOL)on IPF and its relationship with Th1/Th2 shift.Methods:Rats were divided into six groups:control group,model group(bleomycin),pirfenidone group(positive group,54 mg/kg,i.g.)and JBOL(5.4,10.8 and 21.6 mL/kg,i.g.)groups.The rat model was established by an intratracheal instillation of bleomycin(BLM,5 mg/kg).One day after injection of BLM,pirfenidone or JBOL was given to rats once daily within 28 consecutive days,respectively.Positron emission tomography/computed tomography(PET/CT)was performed on the treated rats.The extent of alveolitis and fibrosis was observed by H&E and Masson trichrome staining.The contents of TGF-β1,TNF-α,IL-4 and IFN-γwere further quantified by ELISA assay.Results:PET/CT and histopathological evidence showed the ability of JBOL to attenuate bleomycininduced alveolitis and fibrosis extent,and the alveolitis lesion score was markedly decreased compared with the model group.The increased expression of inflammatory cytokines TGF-β1 and TNF-αinduced by bleomycin was also suppressed by JBOL.The Th1 response was limited by the reduced IFN-γafter BLM administration,and the Th2 response predominated significantly marked by the increased IL-4.JBOL could increase the level of IFN-γand markedly increased the ratio of IFN-γ/IL-4.Conclusion:These findings suggested that JBOL may attenuate BLM-induced idiopathic pulmonary fibrosis via reducing inflammatory cell infiltration,pro-inflammatory cytokine release and excessive collagen deposition in rats.One of the mechanisms is the reversion of Th1/Th2 shift caused by BLM.