Recent investigations on the regulatory action of extracellular vesicles (EVs) on immune cells in vitro and in vivo have sparked interest on the subject. As commonly known, EVs are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles containing exosomes, microvesicles, and apoptotic bodies. They are double-layer membrane-bound vesicles enriched with proteins, nucleic acids, and other active compounds. EVs are recognized as a novel apparatus for intercellular communication that acts through delivery of signal molecules. EVs are secreted by almost all cell types, including stem/progenitor cells. The EVs derived from stem/progenitor cells are analogous to the parental cells and inhibit or enhance immune response. This review aims to provide its readers a comprehensive overview of the possible mechanisms underlying the immunomodulatory effects exerted by stem/progenitor cell-derived EVs upon natural killer (NK) cells, dendritic cells (DCs), monocytes/macrophages, microglia, T cells, and B cells.

Natural killer (NK) cells are critical components of host innate immunity and function as the first line of defense against tumors and viral infection. There is increasing evidence that extracellular vesicles (EVs) are involved in the antitumor activity of NK cells. NK cell-derived EVs (NKEVs) carrying cargo such as cytotoxic proteins, microRNAs, and cytokines employ multiple mechanisms to kill tumor cells, but also exhibit immunomodulatory activity by stimulating other immune cells. Several studies have reported that NKEVs can reverse immune suppression under tolerogenic conditions and contribute to NK-mediated immune surveillance against tumors. Thus, NKEVs are a promising tool for cancer immunotherapy. In this review, we describe the biological effects and potential applications of NKEVs in antitumor immunity.

Extracellular vesicles (EVs) are nanometer-sized and membrane-bound vesicles, including exosomes and microvesicles. EVs can deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types including stem/progenitor cells. Stem/progenitor cell-derived EVs have been identified to exert immunomodulatory effects on target cells through transferring protein molecules as well as regulatory effects on the phenotype of target cells through fusion with the target cells membrane and/or through direct endocytosis by target cells to transfer nucleic acid substances (such as mRNA, miRNA) to the target cells. In both human and animal models, the use of stem/progenitor cells (such as bone marrow mesenchymal stromal cells) has been shown to promote the recovery of kidney diseases such as acute kidney injury and chronic kidney disease. Stem/progenitor cell-derived extracellular vesicles are an important mechanism by which stem/progenitor cells might repair kidney injury. Here, this review will discuss the latest advances concerning the application potential of stem/progenitor cell-derived extracellular vesicles in renal diseases, including the aspects as follows: anti-inflammatory, proliferation-promoting and anti-apoptotic, proangiogenic, antifibrotic and renal cancer progression-promoting. Therefore, stem/progenitor cell-derived extracellular vesicles may be a promising treatment tool for renal diseases.

PurposeTo analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value.MethodA total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers.ResultsIn total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age <1 year or ≥10 years, WB≥50×109/L) in ETV6/RUNX1-positive group was significantly lower than that in negative group (P<0.001), while the proportion of patients with good early response (good response to prednisone, D15 MRD < 0.1%, and D33 MRD < 0.01%) in ETV6/RUNX1-positive group was higher than that in the negative group (P<0.001, 0.788 and 0.004, respectively). Multivariate analysis of 2,530 patients found that age <1 or ≥10 years, SCCLG-ALL-2016 protocol, and MLL were independent predictor of outcome but not ETV6/RUNX1. The EFS and OS of the ETV6/RUNX1-positive group were significantly higher than those of the negative group (3-year EFS: 90.11 ± 4.21% vs 82 ± 2.36%, P<0.0001, 3-year OS: 91.99 ± 3.92% vs 88.79 ± 1.87%, P=0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children.ConclusionsETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment.

Mitochondria participate in immune regulation through various mechanisms, such as changes in the mitochondrial dynamics, as metabolic mediators of the tricarboxylic acid cycle, by the production of reactive oxygen species, and mitochondrial DNA damage, among others. In recent years, studies have shown that extracellular vesicles are widely involved in intercellular communication and exert important effects on immune regulation. Recently, the immunoregulatory effects of mitochondria from extracellular vesicles have gained increasing attention. In this article, we review the mechanisms by which mitochondria participate in immune regulation and exert immunoregulatory effects upon delivery by extracellular vesicles. We also focus on the influence of the immunoregulatory effects of mitochondria from extracellular vesicles to further shed light on the underlying mechanisms.

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Objective: Chemotherapy and hematopoietic stem cell transplantation (HSCT) play important roles in clinical etiology, symptoms, signs, imaging findings, and biochemical parameters for inducing posterior reversible encephalopathy syndrome (PRES) in pediatric oncologic diseases. We aimed to evaluate various risk factors of pediatric oncologic diseases after conducting chemotherapy and HSCT to induce PRES for predicting the clinical prognosis frequency. Methods: The literature was performed on PubMed, Web of Science, and Embase databases to recognize the qualified studies. The odds ratios (ORs) of related risk factors and their corresponding 95% confidence intervals (CIs) were used to compute the pooled assessments of the outcomes. Results: Six studies were included in the meta-analysis, involving 828 records. The risk of female children has a significantly higher incidence than male children in oncologic age groups of PRES. Children over the age of 10 years old in oncologic age groups develop a significantly increased risk of PRES. Acute graft-versus-host disease (GVHD) has a significant promotion effect on the occurrence of PRES. Hypertension can promote the occurrence of PRES in children. The risk of PRES in immunodeficient children increases significantly. Children with sickle cell disease (SCD) have a significantly increased risk of PRES. The risk of PRES in children with T-cell leukemia rises considerably. The central nervous system (CNS) leukemia/involvement has a significant role in promoting the occurrence of PRES in children. The pooled OR for the factors male, ≥10 years old of age, acute GVHD, hypertension, immunodeficiency, SCD, T-cell leukemia, CNS leukemia/involvement was 0.66 (95% CI: 0.58, 0.76; P

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems. Immunopathology believes that abnormal T cell function and excessive production of autoantibodies by B cells are involved in multi-organ damage. Human umbilical cord mesenchymal stem cells (hUCMSCs) therapies have endowed with promise in SLE, while the function of MSC-derived extracellular vesicles (MSC-EVs) was still unclear. Extracellular vesicles (EVs) are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles. EVs play a vital role in cell-to-cell communication by acting as biological transporters. New evidence has shown beneficial effects of MSC-EVs on autoimmune diseases, such as their immunomodulatory properties. In this study, we investigated whether hUCMSCs derived extracellular vesicles (hUCMSC-EVs) could regulate abnormal immune responses of T cells or B cells in SLE. We isolated splenic mononuclear cells from MRL/lpr mice, a classical animal model of SLE. PBS (Phosphate-buffered saline), 2 × 105 hUCMSCs, 25 µg/ml hUCMSC-EVs, 50 µg/ml hUCMSC-EVs were co-cultured with 2 × 106 activated splenic mononuclear cells for 3 days in vitro, respectively. The proportions of CD4+ T cell subsets, B cells and the concentrations of cytokines were detected. Both hUCMSCs and hUCMSC-EVs inhibited CD4+ T cells, increased the production of T helper (Th)17 cells, promoted the production of interleukin (IL)-17 and transforming growth factor beta1 (TGF-β1) (P < 0.05), although they had no significant effects on Th1, Th2, T follicular helper (Tfh), regulatory T (Treg) cells and IL-10 (P > 0.05); only hUCMSCs inhibited CD19+ B cells, promoted the production of interferon-gamma (IFN-γ) and IL-4 (P < 0.05). hUCMSCs exert immunoregulatory effects on SLE at least partially through hUCMSC-EVs in vitro, therefore, hUCMSC-EVs play novel and potential regulator roles in SLE.