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While immunosuppressive environments mediated by myeloid-derived suppressor cells (MDSCs) have been well documented in glioma patients, the mechanisms of MDSC development and activation have not been clearly defined. Here, we elucidated a role for glioma-derived exosomes (GDEs) in potentiating an MDSC pathway. We isolated normoxia-stimulated and hypoxia-stimulated GDEs and studied their MDSC induction abilities in vivo and in vitro. Analyses of spleen and bone marrow MDSC proportions (flow cytometry) and reactive oxygen species (ROS), arginase activity, nitric oxide (NO), T-cell proliferation and immunosuppressive cytokine (IL-10 and TGF-β, ELISA) levels were used to assess MDSC expansion and functional capacity. We also performed microRNA (miRNA) sequencing analysis of two types of GDEs to find miRNAs that potentially mediate the development and activation of MDSCs. GDE miRNA intracellular signaling in MDSCs was also studied. Hypoxia promoted the secretion of GDEs, and mouse MDSCs could uptake GDEs. Hypoxia-stimulated GDEs had a stronger ability to induce MDSCs than N-GDEs. The hypoxia-inducible expression of miR-10a and miR-21 in GDEs mediated GDE-induced MDSC expansion and activation by targeting RAR-related orphan receptor alpha (RORA) and phosphatase and tensin homolog (PTEN). Mice inoculated with miR-10a or miR-21 knockout glioma cells generated fewer MDSCs than those inoculated with normal glioma cells. These data elucidated a mechanism by which glioma cells influence the differentiation and activation of MDSCs via exosomes and demonstrated how local glioma hypoxia affects the entirety of tumor immune environments.

BackgroundThe Body Mass Index (BMI) has long been used as an anthropometric measurement. Waist circumference (WC) and waist-to-height ratio (WHtR) have been proposed as alternatives to BMI. Recently, two new anthropometric indices, the A Body Shape Index (ABSI) and Body Roundness Index (BRI) have been developed as possible improved alternatives to BMI and WC. The main research aim is to assess the capacity of the ABSI and BRI to identify subjects with diabetes mellitus (DM) and the secondary aim is to determine whether ABSI and/or BRI is superior to the traditional body indices (BMI, WC, and WHtR).Methods and ResultsThis cross-sectional study was conducted in the rural areas of northeast China from January 2012 to August 2013, and the final analysis included data obtained form 5253 men and 6092 women. 1182 participants (10.4 %) suffered from DM. Spearman rank test showed that BRI and WHtR showed the highest Spearman correlation coefficient for DM whereas ABSI showed the lowest. The prevalence of DM increased across quartiles for ABSI, BMI, BRI, WC and WHtR. A multivariate logistic regression analysis of the presence of DM for the highest quartile vs. the lowest quartile of each anthropometric measure, showed that the WHtR was the best predictor of DM (OR: 2.40, 95 % CI: 1.42–3.39 in men; OR: 2.67, 95 % CI: 1.60–3.74 in women, both P < 0.001), and the ABSI was the poorest predictor of DM (OR: 1.51, 95 % CI: 1.05–1.97 in men; OR: 1.55, 95 % CI: 1.07–2.04 in women, both P < 0.05). ABSI showed the lowest AUCs (AUC: 0.61, 95 % CI: 0.58–0.63 for men; AUC: 0.61, 95 % CI: 0.59–0.63 for women) for DM in both sexes, while BRI (AUC: 0.66, 95 % CI: 0.63–0.68 for men; AUC: 0.67, 95 % CI: 0.65–0.69 for women) had high AUCs for DM that equaled those of WHtR.ConclusionsOur results showed neither ABSI nor BRI were superior to BMI, WC, or WHtR for predicting the presence of DM. ABSI showed the weakest predictive ability, while BRI showed potential for use as an alternative obesity measure in assessment of DM.