Recent studies have shown that extracellular microRNAs are not only potential biomarkers but are also involved in cell interactions to regulate the intercommunication between cancer cells and their microenvironments in various types of malignancies. In this study, we isolated exosomes from nasopharyngeal carcinoma (NPC) cell lines and patient sera (T-EXOs), or control NP69 cells and healthy donor sera (HD-EXOs). We found that miR-24-3p was markedly enriched in T-EXOs as compared with HD-EXOs; the serum exosomal miR-24-3p level was correlated with worse disease-free survival of patients (p < 0.05). Knockdown of exosomal miR-24-3p (miR-24-3p-sponge-T-EXOs) by a sponge RNA targeting miR-24-3p restored the T-EXO-mediated (control-sponge-T-EXO) inhibition of T-cell proliferation and Th1 and Th17 differentiation, and the induction of regulatory T cells (Tregs). Mechanistic analyses revealed that administration of exosomal miR-24-3p increased P-ERK, P-STAT1 and P-STAT3 expression while decreasing P-STAT5 expression during T-cell proliferation and differentiation. Moreover, by in vivo and in vitro assessments, we found FGF11 to be a direct target of miR-24-3p. However, both miR-24-3p-sponge-T-EXOs and T-EXOs (control-sponge-T-EXOs) impeded proliferation and Th1 and Th17 differentiation, but induced Treg differentiation, of lenti-shFGF11-transfected T cells. The levels of phosphorylated ERK and STAT proteins were different in lenti-ScshRNA-transfected T cells and lenti-shFGF11-transfected T cells following administration of miR-24-3p-sponge-T-EXO. Interestingly, tumour FGF11 expression was positively correlated with the number of CD4 and CD8 T cells in vivo, and predicted favourable patient DFS (p < 0.05). Additionally, hypoxia increased cellular and exosomal miR-24-3p levels and enhanced the inhibitory effect of T-EXO on T-cell proliferation and differentiation. Collectively, our findings suggest that exosomal miR-24-3p is involved in tumour pathogenesis by mediating T-cell suppression via repression of FGF11, and may serve as a potential prognostic biomarker in NPC. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Stimulator of interferon genes (STING), a major adaptor protein in antiviral innate immune signaling, is considered as one of the most important regulators of antiviral and antitumor immunity. Although STING agonists are now intensively studied in clinical trials as a new class of adjuvants to boost cancer immunotherapy, the tumor-intrinsic role of the STING pathway in shaping the tumor microenvironment remains controversial. Here, we discovered that STING plays a vital role in regulation of myeloidderived suppressor cell (MDSC) differentiation and antitumor immunity in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). Mechanistic analyses reveal that STING represses NPC-derived MDSC induction by enhancing SOCS1 expression in both tumor cells and MDSCs. SOCS1 physically interacts with STAT3 through its SH2 domain to prevent STAT3 phosphorylation and dimerization, resulting in reduced MDSC induction via inhibition of GM-CSF and IL-6 production. Notably, reduced tumoral STING expression was found to be significantly associated with a poor prognosis for NPC patients. Our findings reveal a novel mechanism linking STING to tumor microenvironmental cytokine production and MDSC induction.

Optogenetics play a significant role in neuroscientific research by providing a tool for understanding neural circuits and brain functions. Natronomonas pharaonis halorhodopsin (NpHR) actively pumps chloride ions into the cells and hyperpolarizes neuronal membranes in response to yellow light. In this study, we generated transgenic Drosophila expressing NpHR under the control of the Gal4/UAS system and virus-infected mice expressing NpHR to explore the effect of dendritic cell factor 1 (Dcf1) on the behavior mediated by the mushroom body in Drosophila and the dentate gyrus (DG) in mice. Study of optogenetic behavior showed that NpHR suppressed the behavior in Drosophila larvae and mice, whereas Dcf1 rescued this suppression. These results suggest that Dcf1 plays an important role in behavior induced by the mushroom body and the hippocampus and provides novel insights into their functions. J. Cell. Biochem. 118: 4210-4215, 2017. © 2017 Wiley Periodicals, Inc.