Hepatocellular carcinoma (HCC) remains a global challenge due to high morbidity and mortality rates and poor response to treatment. Immunotherapy, based on introduction of dendritic cells (DCs) activated by tumor cell lysates as antigens ex vivo, shows limited response rates in HCC patients. Here, we demonstrate that tumor cell-derived exosomes (TEXs), displaying an array of HCC antigens, can elicit a stronger immune response than cell lysates in vitro and in vivo. Significant tumor growth inhibition was achieved in ectopic and orthotopic HCC mice treated with TEX-pulsed DCs. Importantly, the tumor immune microenvironment was significantly improved in orthotopic HCC mice treated by TEX-pulsed DCs, demonstrated by increased numbers of T lymphocytes, elevated levels of interferon-c, and decreased levels of interleukin-10 and tumor growth factor-b in tumor sites. As expected, T cells played an essential role in the TEX-pulsed DC-mediated immune response. Notably, exosomes from HCC cells not only promoted HCC-specific cytolysis but also provided cross-protective effects against pancreatic cancer cells. Moreover, HCC-specific cytolysis, elicited by DCs pulsed with human HepG2 cellderived exosomes, was observed across different human HCC cells irrespective of human leukocyte antigen types. Conclusion: HCC TEXs can potently carry HCC antigens, trigger a strong DC-mediated immune response, and improve the HCC tumor microenvironment. (HEPATOLOGY 2016;64:456-472) R anked as the sixth most lethal malignancy, hepatocellular carcinoma (HCC) attracts significant attention due to its aggressive nature, high mortality rate, and low response rates to treatments in the clinic.(1) Although surgical resection can extend the life span of HCC patients, it is only amenable to early-stage HCC patients and has a high recurrence rate that is far from ideal. Chemotherapeutic or radiotherapeutic interventions such as sorafenib, transcatheter arterial chemoembolization, and radiofrequency ablation are intensively used in the clinic; however, the survival benefit is limited.(2) Therefore, other interventional approaches have been rigorously pursued. Among these, dendritic cell (DC)-based immunotherapy is a promising strategy with clinical studies in humans. (3)(4)(5) The first-in-human clinical trial among HCC patients demonstrated proof-of-concept evidence for DC-based immunotherapy with HCC cell lysates as antigens; however, the response rate was marginal and the efficacy was low, (5) necessitating further investigation into other immunotherapy options.Recently, the discovery of physiological roles of the exosome, a nanovesicle secreted by cells, as an intercellular courier of protein, messenger RNA, and micro-RNA, has garnered considerable interest.(6) Exosomes have been extensively studied for diagnostic purposes

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Objectives Diabetic wound healing remains a global challenge in the clinic and in research. However, the current medical dressings are difficult to meet the demands. The primary goal of this study was to fabricate a functional hydrogel wound dressing that can provide an appropriate microenvironment and supplementation with growth factors to promote skin regeneration and functional restoration in diabetic wounds. Materials and Methods Small extracellular vesicles (sEVs) were bound to the porcine small intestinal submucosa‐based hydrogel material through peptides (SC‐Ps‐sEVs) to increase the content and achieve a sustained release. NIH3T3 cell was used to evaluate the biocompatibility and the promoting proliferation, migration and adhesion abilities of the SC‐Ps‐sEVs. EA.hy926 cell was used to evaluate the stimulating angiogenesis of SC‐Ps‐sEVs. The diabetic wound model was used to investigate the function/role of SC‐Ps‐sEVs hydrogel in promoting wound healing. Results A functional hydrogel wound dressing with good mechanical properties, excellent biocompatibility and superior stimulating angiogenesis capacity was designed and facilely fabricated, which could effectively enable full‐thickness skin wounds healing in diabetic rat model. Conclusions This work led to the development of SIS, which shows an unprecedented combination of mechanical, biological and wound healing properties. This functional hydrogel wound dressing may find broad utility in the field of regenerative medicine and may be similarly useful in the treatment of wounds in epithelial tissues, such as the intestine, lung and liver.