Variations of circulating endothelial progenitor cells and transforming growth factor-beta-1 (TGF-β1) during thoracic radiotherapy are predictive for radiation pneumonitis

Abstract

BackgroundThe vascular endothelial cells are important targets of radiotherapy, which may be involved in the pathogenesis of radiation pneumonitis (RP). This study investigated the variations of circulating endothelial progenitor cells (EPCs) and transforming growth factor-beta-1 (TGF-β1) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non–small-cell lung cancer (NSCLC) and analyzed the correlation between these variations with the occurrence of RP.Patients and methodsFrom November 2008 to November 2009, eighty-four consecutive patients receiving 3D-CRT for stage III disease were evaluated prospectively. Circulating EPCs and TGF-β1 levels were measured at baseline, every 2 weeks during, and at the end of treatment. RP was evaluated prospectively at 6 weeks after 3D-CRT.ResultsThirty-eight patients (47.5%) experienced score 1 or more of RP. The baseline levels of EPCs and TGF-β1 were analyzed, no difference was found between patients with and without RP during and after 3D-CRT. By serial measurement of TGF-β1 and EPCs levels, we found that the mean levels of EPCs in the whole population remained stable during radiotherapy, but the mean levels of TGF-β1 increased slowly during radiotherapy. TGF-β1 and EPCs levels were all significantly higher at week 2, week 4 and week 6 in patients with RP than that in patients without RP, respectively. During the period of radiation treatment, TGF-β1 levels began to increase in the first 2 weeks and became significantly higher at week 6 (P < 0.01). EPCs levels also began to increase in the first 2 weeks and reached a peak at week 4. Using an ANOVA model for repeated-measures, we found significant associations between the levels of TGF-β1 and EPCs during the course of 3D-CRT and the risk of developing RP (P < 0.01). Most of the dosimetric factors showed a significant association with RP.ConclusionEarly variations of TGF-β1 and EPCs levels during 3D-CRT are significantly associated with the risk of RP. Variations of circulating TGF-β1 and EPCs levels during 3D-CRT may serve as independent predictive factors for RP.Trial registrationTrials registration number: 20070618

TGFβ Inhibition Prior to Hypofractionated Radiation Enhances Efficacy in Preclinical Models

“…In addition, TGFb promotes alternative macrophage differentiation and decreases antigen presentation and effector function, while increasing macrophage trafficking to the site of inflammation (23,24). TGFb inhibitors have been combined with radiotherapy in preclinical cancer models and have increased radiosensitivity and reduced radiation-related mucositis, pneumonitis, and fibrosis (25)(26)(27)(28)(29)(30).…”

Stereotactic Ablative Radiation Therapy Combined With Immunotherapy for Solid Tumors

“…34,47–54 Ways of evoking abscopal effects are now the topic of numerous trials throughout the world. Although preclinical data suggest that local irradiation can have modest immunosuppressive effects such as increasing transforming growth factor β 55 and increasing proportions of regulatory T cells (T regs ) 56 and myeloid- derived suppressor cells (MDSCs), 57,58 it also has immune-stimulatory effects such as enhancing T-cell priming. 36–41,59–62 Indeed, radiation enhances the immunogenicity of tumors through numerous mechanisms, and this heightened visibility and susceptibility to the immune system cause a high-amplitude local immune response that can then spread and take effect at other, more distant sites when combined with immunotherapy.…”

Experimental study of endothelial progenitor cells labeled with superparamagnetic iron oxide in vitro

“…Studies have reported the number of circulating EPCs was significantly increased under several pathological conditions that involved vascular injury or instability, including myocardial infarction and cancer (10,11). This therefore suggested that circulating EPCs may have provided an endogenous repair mechanism that counteracted the ongoing risk factor-induced endothelial injury and therefore protected against the development of vascular injuries, such as myocardial infarction (10)(11)(12)(13). Therefore, the present study hypothesized that changes in circulating levels of EPCs may act as a predictor for the incidence of acute myocardial infarction.…”