Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73+γδ1 Treg cells

γδT cells have been reported to exert immunosuppressive functions in multiple solid malignant diseases,but their immunosuppressive functional subpopulation in breast cancer(BC)is still undetermined.Here,we collected 40 paired BC and normal tissue samples from Chinese patients for analysis.First,we showed thatγδT1 cells comprise the majority of CD3+T cells in BC;next,we found that CD73+γδT1 cells were the predominant regulatory T-cell(Treg)population in BC,and that their prevalence in peripheral blood was also related to tumour burden.In addition,CD73+γδT1 cells exert an immunosuppressive effect via adenosine generation.We also found that BC could modulate CD73 expression onγδT cells in a non-contact manner.The microarray analysis and functional experiments indicated that breast tumour cell-derived exosomes(TDEs)could transmit lncRNA SNHG16,which upregulates CD73 expression,to Vδ1 T cells.Regarding the mechanism,SNHG16 served as a ceRNA by sponging miR-16–5p,which led to the derepression of its target gene SMAD5 and resulted in potentiation of the TGF-β1/SMAD5 pathway to upregulate CD73 expression in Vδ1 T cells.Our results showed that the BC-derived exosomal SNHG16/miR-16–5p/SMAD5-regulatory axis potentiates TGF-β1/SMAD5 pathway activation,thus inducing CD73 expression in Vδ1 T cells.Our results first identify the significance of CD73+Vδ1 Tregs in BC,and therapy targeting this subpopulation or blocking TDEs might have potential for BC treatment in the future.

Flexible electrical stimulation device with Chitosan-Vaseline®dressing accelerates wound healing in diabetes

The healing process of diabetic wounds is typically disordered and prolonged and requires both angiogenesis and epithelialization.Disruptions of the endogenous electric fields(EFs)may lead to disordered cell migration.Electrical stimulation(ES)that mimics endogenous EFs is a promising method in treating diabetic wounds;however,a microenvironment that facilitates cell migration and a convenient means that can be used to apply ES are also required.Chitosan-Vaseline■gauze(CVG)has been identified to facilitate wound healing;it also promotes moisture retention and immune regulation and has antibacterial activity.For this study,we created a wound dressing using CVG together with a flexible ES device and further evaluated its potential as a treatment for diabetic wounds.We found that high voltage monophasic pulsed current(HVMPC)promoted healing of diabetic wounds in vivo.In studies carried out in vitro,we found that HVMPC promoted the proliferation and migration of human umbilical vein endothelial cells(HUVECs)by activating PI3K/Akt and ERK1/2 signaling.Overall,we determined that the flexible ES-chitosan dressing may promoted healing of diabetic wounds by accelerating angiogenesis,enhancing epithelialization,and inhibiting scar formation.These findings provide support for the ongoing development of this multidisciplinary product for the care and treatment of diabetic wounds.