Qingqing Liu

Endoplasmic reticulum (ER) stress promotes tumor cell escape from immunosurveillance. However, the underlying mechanisms remain unknown. We hypothesized that ER stress induces hepatocellular carcinoma (HCC) cells to release exosomes, which attenuate antitumor immunity by modulating the expression of programmed death ligand 1 (PD‐L1) in macrophages. In this study, we demonstrated that expression of several ER stress markers (glucose‐regulated protein 78, activating transcription factor 6, protein kinase R–like ER kinase, and inositol‐requiring enzyme 1α) was up‐regulated in HCC tissues and negatively correlated with the overall survival and clinicopathological scores in patients with HCC. Expression of ER stress–related proteins positively correlated with CD68 + macrophage recruitment and PD‐L1 expression in HCC tissues. High‐throughput sequencing analysis identified miR‐23a‐3p as one of the most abundant microRNAs in exosomes derived from tunicamycin (TM)‐treated HCC cells (Exo‐TMs). miR‐23a‐3p levels in HCC tissues negatively correlated with overall survival. Treatment with Exo‐TMs up‐regulated the expression of PD‐L1 in macrophages in vitro and in vivo . Bioinformatics analysis suggests that miR‐23a‐3p regulates PD‐L1 expression through the phosphatase and tensin homolog (PTEN)–phosphatidylinositol 3‐kinase–protein kinase B (AKT) pathway. This notion was confirmed by in vitro transfection and coculture experiments, which revealed that miR‐23a‐3p inhibited PTEN expression and subsequently elevated phosphorylated AKT and PD‐L1 expression in macrophages. Finally, coculture of T cells with Exo‐TM–stimulated macrophages decreased CD8 + T‐cell ratio and interleukin‐2 production but increased T‐cell apoptosis in vitro . Conclusion : ER‐stressed HCC cells release exosomes to up‐regulate PD‐L1 expression in macrophages, which subsequently inhibits T‐cell function through an exosome miR‐23a–PTEN–AKT pathway. Our findings provide insight into the mechanism how tumor cells escape from antitumor immunity.

In the past decade, it was a significant trend for surveillance applications to send huge amounts of real-time media data to the cloud via dedicated high-speed fiber networks. However, with the explosion of mobile devices and services in the era of Internet-of-Things, it becomes more promising to undertake real-time data processing at the edge of the network in a distributed way. Moreover, in order to reduce the investment of network deployment, media communication in surveillance applications is gradually changing to be wireless. It consequently poses great challenges to detect objects at the edge in a distributed and communication-efficient way. In this article, we propose an edge computing based object detection architecture to achieve distributed and efficient object detection via wireless communications for real-time surveillance applications. We first introduce the proposed architecture as well as its potential benefits, and identify the associated challenges in the implementation of the architecture. Then, a case study is presented to show our preliminary solution, followed by performance evaluation results. Finally, future research directions are pointed out for further studies.

Immunosuppression is a significant factor in the progression of tumor invasion and metastasis. Melatonin, a well-known hormone, has certain cytotoxic and immune regulatory effects to inhibit tumor function. Exosomes are small membrane vesicles released by many kinds of cells, which contain different macromolecules, such as mRNAs and microRNAs (miRNAs), and proteins that can mediate communications between cells. Tumor-derived exosomes may cause immunosuppression, however, it is unknown whether melatonin can attenuate an immunosuppressive status by altering the function of tumor-derived exosomes. In the present study, we evaluated the effects of hepatocellularcarcinoma-derived exosomes (Exo-con) and exosomes derived from hepatocellularcarcinoma cells treated with 0.1 mM melatonin (Exo-MT), on the expression of inflammatory factors and programmed death ligand 1(PD-L1) by co-culturing Exo-con and Exo-MT, respectively, with macrophages differentiated from THP-1 cells or RAW264.7 cells. Our in vitro results indicate that Exo-MT can downregulate the expression of PD-L1 on macrophages while Exo-con can upregulate the expression of PD-L1 through flow cytometry and immunofluorescence analysis. In addition, Exo-con upregulates the secretion of cytokines, such as IL-6, IL-10, IL-1, and TNF- in macrophages. Accordingly, Exo-MT could attenuate the high expression of these inflammatory cytokines. Furthermore, in vivo experiments confirmed the results found in vitro. PD-L1 expression and cytokine secretion were lower in the Exo-MT group compared with those in the Exo-con group. Working to identify a specific mechanism, our research shows that Exo-MT decreases STAT3 activation compared to the Exo-con group. In summary, we found exosomes from melatonin treated hepatocellularcarcinoma cells alters the immunosupression status through STAT3 pathway in macrophages. Our study may provide a new avenue to investigate the mechanisms of melatonin in regulating an immunosuppressive status.