Background: Myeloid-derived suppressor cells (MDSCs) promote immunosuppression in the tumor microenvironment, support tumor growth and survival, and may contribute to immunotherapy resistance. Recent studies showed that tumor-derived exosomes (TDEs) can induce MDSCs accumulation and expansion, the mechanisms of which are largely unknown. Methods: The morphologies and sizes of the exosomes was observed by using a JEM-1400 transmission electron microscope. MicroRNA(miR)-107 and ARG1 , DICER1 , PTEN , PI3K , AKT , mTOR , and NF-kB mRNAs were quantified by quantitative reverse tanscription PCR. Dual-Luciferase Reports Assay were used to examine the expression of genes which was targeted by miR-107. The expression of proteins were analyzed by using western blot. Results: MiR-107 was not only overexpressed in gastric cancer cells but also enriched in their secreted TDEs. Also, these miR-107 enriched TDEs could be taken up by HLA-DR - CD33 + MDSCs, where miR-107 was able to target and suppress expression of DICER1 and PTEN genes. Dampened DICER1 expression supported expansion of MDSCs , while decreased PTEN led to activation of the PI3K pathway, resulting in increased ARG1 expression. Furthemore, gastric cancer-derived miR-107 TDEs, when dosed intravenously into mice, were also capable of inducing expansion of CD11b + Gr1 +/high MDSCs in mouse peripheral blood and altering expression of DICER1 , PTEN , ARG1 , and NOS2 in the MDSCs. Conclusions: Our findings demonstrate for the first time that gastric cancer-secreted exosomes are able to deliver miR-107 to the host MDSCs where they induce their expansion and activition by targeting DICER1 and PTEN genes, thereby may provide novel cancer therapeutics target for gastric cancer.

Exosomes are extracellular vesicles secreted by a variety of living cells, which have a certain degree of natural targeting as nano-carriers. Almost all exosomes released by cells will eventually enter the blood circulation or be absorbed by other cells. Under the action of content sorting mechanism, some specific surface molecules can be expressed on the surface of exosomes, such as tetraspanins protein and integrin. To some extent, these specific surface molecules can fuse with specific cells, so that exosomes show specific cell natural targeting. In recent years, exosomes have become a drug delivery system with low immunogenicity, high biocompatibility and high efficacy. Nucleic acids, polypeptides, lipids, or small molecule drugs with therapeutic function are organically loaded into exosomes, and then transported to specific types of cells or tissues in vivo, especially tumor tissues, to achieve targeting drug delivery. The natural targeting of exosome has been found and recognized in some studies, but there are still many challenges in effective clinical treatments. The use of the natural targeting of exosomes alone is incapable of accurately transporting the goods loaded to specific sites. Besides, the natural targeting of exosomes is still an open question in disease targeting and efficient gene/chemotherapy combined therapy. Engineering transformation and modification on exosomes can optimize its natural targeting and deliver the goods to a specific location, providing wide use in clinical treatment. This review summarizes the research progress of exosomal natural targeting and transformation strategy of obtained targeting after transformation. The mechanism of natural targeting and obtained targeting after transformation are also reviewed. The potential value of exosomal targeting in clinical application is also discussed. Graphical abstract

The Mainland Chinese IBDQ proved to be a valid, discriminative, and reliable instrument for assessing health-related quality of life in patients with UC and CD in Mainland China.

The results suggest that any interventions that produce a stable clinical remission, whether medical or surgical, allowing patients to return to their usual work position can decrease the disease impact on their daily lives.