No abstract

Tumor-induced, myeloid-derived suppressor cells (MDSCs)-mediated immune dysfunction is an important mechanism that leads to tumor immune escape and the inefficacy of cancer immunotherapy. Importantly, tumor-infiltrating MDSCs have much stronger ability compared to MDSCs in the periphery. However, the mechanisms that tumor microenvironment induces the accumulation and function of MDSCs are poorly understood. Here, we report that Interleukin-33 (IL-33) - a cytokine which can be abundantly released in tumor tissues both in 4T1-bearing mice and breast cancer patients, is crucial for facilitating the expansion of MDSCs. IL-33 in tumor microenvironment reduces the apoptosis and sustains the survival of MDSCs through induction of autocrine secretion of GM-CSF, which forms a positive amplifying loop for MDSC accumulation. This is in conjunction with IL-33-driven induction of arginase-1 expression and activation of NF-κB and MAPK signaling in MDSCs which augments their immunosuppressive ability, and histone modifications were involved in IL-33 signaling in MDSCs. In ST2 mice, the defect of IL-33 signaling in MDSCs attenuates the immunosuppressive and pro-tumoral capacity of MDSCs. Our results identify IL-33 as a critical mediator that contributes to the abnormal expansion and enhanced immunosuppressive function of MDSCs within tumor microenvironment, which can be potentially targeted to reverse MDSC-mediated tumor immune evasion.

Background Stroke is the leading cause of death and years of life lost in China, and this problem is growing because stroke risk factors such as hypertension and hypercholesteremia have been on the rise as China experiences the demographic transition. The Chinese government has created public health initiatives in the form of guidelines, policies and programs to combat this problem, but the dissemination and effectiveness of these policies are not well known. Aims The aim of this study was to determine trends in stroke incidence, prevalence, and stroke-related mortality in China and to report these trends in the context of stroke initiatives that have been enacted by the Chinese government. Summary of review We systematically reviewed articles on stroke rates and stroke initiatives from 1980 to 2017. A meta-regression including 11 studies showed that stroke incidence remained stable at 128.3 per 100,000 per year from 1980 to 2005 and has increased by 21.3 per 100,000 per year since then to 298.7 per 100,000 per year in 2013. A meta-regression including seven studies demonstrated a gradual decline in stroke-related mortality by 6.5 per 100,000 per year since 1980 (a decline from 369.2 in 1980 to 154.7 per 100,000 per year in 2013). Average stroke prevalence was 898.4 per 100,000 over the entire time-period. Limitations included heterogeneity between the studies. We identified 12 stroke initiatives, the first of which was enacted in 2006. Conclusions Despite numerous public health initiatives aimed at combating stroke that started in 2006, stroke incidence in China has increased over the last decade, likely as a result of aging and urbanization of the Chinese population.

Background Circular RNAs (circRNAs), which are endogenous non-coding RNAs, are associated with various biological processes including development, homeostatic maintenance, and pathological responses. Accumulating evidence has implicated non-coding RNAs in cancer progression, and the role of circRNAs in particular has drawn wide attention. However, circRNA expression patterns and functions in hepatocellular carcinoma (HCC) remain poorly understood. Methods CircRNA sequencing was performed to screen differentially expressed circRNAs in HCC. Northern blotting, quantitative real-time polymerase chain reaction, nucleocytoplasmic fractionation, and fluorescence in situ hybridization analyses were conducted to evaluate the expression and localization of circSLC7A11 in HCC tissues and cells. CircSLC7A11 expression levels were modified in cultured HCC cell lines to explore the association between the expression of circSLC7A11 and the malignant behavior of these cells using several cell-based assays. The modified cells were implanted into immunocompetent nude mice to assess tumor growth and metastasis in vivo. We applied bioinformatics methods, RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays to explore the mechanisms of circSLC7A11 in HCC. Results CircSLC7A11 (hsa_circ_0070975) was conserved and dramatically overexpressed in HCC tissues and cells. HCC patients showing high circSLC7A11 expression had worse prognoses. Our in vitro and in vivo experiments showed that circSLC7A11 markedly accelerated HCC progression and metastasis through the circSLC7A11/miR-330-3p/CDK1 axis. Conclusions The acceleration of HCC progression and metastasis by circSLC7A11 through the circSLC7A11/miR-330-3p/CDK1 axis suggests that circSLC7A11 is a potential novel diagnostic and therapeutic target for HCC treatment.