Background
Recurrence and metastasis are the leading causes of tumour-related death in patients with oesophageal squamous cell carcinoma (ESCC). Tumour-infiltrating natural killer cells (NK cells) display powerful cytotoxicity to tumour cells and play a pivotal role in tumour therapy. However, the phenotype and functional regulation of NK cells in oesophageal squamous cell carcinoma (ESCC) remains largely unknown.
Methods
Single cell suspensions from blood and tissue samples were isolated by physical dissociation and filtering through a 70 μm cell strainer. Flow cytometry was applied to profile the activity and function of NK cells, and an antibody chip experiment was used to identify and quantitate cytokine levels. We studied IL-6 and IL-8 function in primary oesophageal squamous carcinoma and NK cell co-cultures in vitro and by a xenograft tumour model in vivo. Western blotting was used to quantitate STAT3 (signal transducer and activator of transcription 3) and p-STAT3 levels. Finally, we performed an IHC array to analyse IL-6/IL-8 (interleukin 6/interleukin 8) expression in 103 pairs of tumours and matched adjacent tissues of patients with ESCC to elucidate the correlation between IL-6 or IL-8 and clinical characteristics.
Results
The percentages of NK cells in both peripheral blood and tumour tissues from patients with ESCC were significantly increased in comparison with those in the controls and correlated with the clinical characteristics. Furthermore, the decrease in activating receptors and increase in inhibitory receptors on the surface of tumour-infiltrating NK cells was confirmed by flow cytometry. The level of granzyme B, the effector molecule of tumour-infiltrating NK cells, was also decreased. Mechanistically, primary ESCC cells activated the STAT3 signalling pathway on NK cells through IL-6 and IL-8 secretion, leading to the downregulation of activating receptors (NKp30 and NKG2D) on the surface of NK cells. An ex vivo study showed that blockade of STAT3 attenuated the IL-6/IL-8-mediated impairment of NK cell function. Moreover, the expression of IL-6 or IL-8 in tumour tissues was validated by immunohistochemistry to be positively correlated with tumour progression and poor survival, respectively.
Conclusions
Tumour cell-secreted IL-6 and IL-8 impair the activity and function of NK cells via STAT3 signalling and contribute to oesophageal squamous cell carcinoma malignancy.
Electronic supplementary material
The online version of this article (10.1186/s13046-019-1310-0) contains supplementary material, which is available to authorized users.
Purpose: To assess the overall diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) in detecting bone metastases with a meta-analysis.
Materials and Methods:The MEDLINE, EMBASE, Cancerlit, and Cochrane Library databases were searched from January 1995 to September 2010 for studies evaluating the accuracy of WB-MRI in detecting bone metastases. Histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months was assessed. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver-operating characteristics.Results: A total of 11 studies with 495 patients who fulfilled all of the inclusion criteria were considered for the analysis. No publication bias was found. WB-MRI had a pooled sensitivity of 0.899 (95% confidence interval [CI], 0.845-0.939) and a pooled specificity of 0.918 (95% CI, 0.882-0.946). The subgroup without diffusion-weighted imaging (DWI) positive results had higher pooled specificity 0.961 (95% CI, 0.922-0.984) than the subgroup with DWI (P < 0.05).Conclusion: WB-MRI was an accurate, cost-effective tool in detecting bone metastases. WB-MRI without DWI may improve the specificity of detecting bone metastases. DWI seems to be a sensitive but rather unspecific modality for the detection of bone metastatic disease. High-quality prospective studies regarding WB-MRI in detecting bone metastases still need to be conducted.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.