本周hzangs在最新文献中选取了7篇分享给大家，第1篇文章介绍了前列腺癌细胞释放外泌体通过PD-1来增强免疫抑制细胞活性，促进免疫逃逸；第2篇文章介绍了细胞外囊泡在脂肪-肿瘤细胞通讯和代谢性疾病中的作用；第3篇文章介绍了神经节苷脂对细胞外囊泡的调控作用；第5篇文章介绍了阿克曼氏菌通过细胞外囊泡调控应激反应影响肿瘤进展。
1. Prostate Cancer Cells Secrete PD-1 in Exosomes to Enhance Myeloid-Derived Suppressor Cell Activity and Promote Tumor Immune Evasion.
前列腺癌细胞在外泌体中分泌 PD-1 以增强髓系来源的抑制细胞活性并促进肿瘤免疫逃逸。
[Cancer Res] PMID: 40698651
Abstract: PD-1 restrains effective killing of cancer cells by the immune system and is predominantly located on the surface of T cells or other immune cells. However, cancer cells also express PD-1 to varying degrees, which is commonly associated with a poor prognosis. In this study, we investigated the regulation and function of PD-1 expression in prostate cancer and revealed the impact on the tumor microenvironment. PD-1 expression in cancer cells positively correlated with Gleason grade and metastasis but negatively correlated with CD8+ T-cell infiltration in patients with prostate cancer. Prostate cancer cells secreted PD-1 in exosomes that enhanced the activity of myeloid-derived suppressor cells by activating JAK/STAT3 signaling. The activated myeloid-derived suppressor cells in turn reduced the infiltration of CD8+ T cells within the tumor, promoting tumor immune evasion. The ubiquitin-specific peptidase 7 (USP7) induced deubiquitination and elevated the abundance of PD-1 in prostate cancer, and USP7 inhibition sensitized prostate cancer tumors to anti-PD-1 antibody treatment. Given the modest efficacy of current immunotherapeutic approaches for prostate cancer, strategies to inhibit the secretion of PD-1-bearing exosomes or USP7 function may emerge as promising immunostimulatory interventions for treating prostate cancer.
2. Extracellular Vesicles and the lipid messengers: The adipose tissue connection to cancer and metabolic disease.
细胞外囊泡和脂质信使：脂肪组织与癌症和代谢疾病的联系。
[Semin Cancer Biol] PMID: 40975244
Abstract: Adipose tissue is essential for maintaining metabolic balance by serving as a major lipid depot for energy storage and release, while also secreting adipokines and extracellular vesicles that regulate inflammation and insulin sensitivity. The lipidic content of adipose tissue not only supports energy homeostasis but also contributes to its inflammatory profile, with altered lipid composition being a key factor in the pathogenesis of metabolic diseases such as obesity, type 2 diabetes, and cardiovascular disorders. Moreover, adipose tissue-derived extracellular vesicles, enriched in lipids, have emerged as significant mediators of intercellular communication, influencing local and systemic processes, including tumor progression. Adipose tissue-derived extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication, with increasing evidences describing their role in microenvironment communication. In this review, we explore the diverse lipid species identified within EVs and examine lipidomics as a powerful and emerging technique to decode their functional roles. By analyzing the lipid cargo of these vesicles, we highlight their potential influence on cancer progression and cardiovascular disease. Furthermore, we discuss the broader implications of EV-derived lipids in metabolic regulation and disease pathophysiology. Understanding the complex interplay between EV lipid composition and pathological processes could open new avenues for biomarker discovery and therapeutic interventions in oncology and cardiovascular medicine.
3. Gangliosides modulate the secretion of extracellular vesicles and their misfolded protein cargo.
神经节苷脂调节细胞外囊泡及其错误折叠蛋白质货物的分泌。
[Sci Adv] PMID: 40961208
Abstract: Gangliosides are glycosphingolipids with important roles in cell signaling and neuroprotection. While present on extracellular vesicles (EVs)-key mediators of intercellular communication-their role in EV biogenesis remains unclear. Here, we identify gangliosides as key modulators of EV biogenesis, with the specific composition of their glycan headgroup and the presence or absence of sialic acid andN-acetyl-d-galactosamine residues dictating whether they promote or inhibit EV biogenesis. GM1 and other complex gangliosides enhance EV secretion, while disruption of ganglioside synthesis impairs it. GM1 supplementation restores EV secretion in Huntington's disease (HD) fibroblasts and cell models with ganglioside deficiency, including models of neurodegenerative diseases caused by a genetic block of ganglioside synthesis. Notably, GM1 enhances EV-mediated secretion of pathogenic misfolded proteins, including mutant huntingtin (mHTT), α-synuclein, and tau, reducing intracellular burden and providing mechanistic insight into the mHTT-lowering effects of GM1 in HD models. Our findings shed light on the neuroprotective roles of gangliosides and their therapeutic potential in misfolded protein disorders.
4. Hybridoma-inspired strategy crafts tailored multifunctional exosomes for precision therapy.
受杂交瘤启发的策略可制作定制的多功能外泌体用于精准治疗。
[Proc Natl Acad Sci U S A] PMID: 40924460
Abstract: Engineering functional exosomes represents a cutting-edge approach in biomedicine, holding the promise to transform targeted therapy. However, challenges such as achieving consistent modification and scalability have limited their wider adoption. Herein, we introduce a universal and effective strategy for engineering multifunctional exosomes through cell fusion. The hybrid-cell-derived exosomes could combine the functional properties of both parental cells and be readily produced by passaging. This method enables customization and large-scale production of exosomes with specific functionalities, potentially advancing precision therapies across a wide array of diseases. As demonstrated in Alzheimer's disease (AD) models, exosomes derived from hybrid cells (HCs) (H/Exos) of mesenchymal stem cells (MSCs) and neutrophils efficiently targeted AD-affected areas via LFA-1/ICAM-1 and improved the cognition of AD mice. Beyond directly promoting neural repair and inhibiting inflammation, we surprisingly found that H/Exos increased microglia abundance, modulated microglia gene expression, enhanced the endocytic and lysosomal function, and promoted microglial phagocytic phenotypic differentiation to clear Aβ. This hybridoma-inspired strategy offers a versatile and practical way to engineer exosomes with desired therapeutic functions, representing a promising direction for personalized therapies.
5. Akkermansia muciniphila ameliorates chronic stress-induced colorectal tumor growth by releasing outer membrane vesicles.
Akkermansia muciniphila 通过释放外膜囊泡来改善慢性应激引起的结直肠肿瘤生长。
[Gut Microbes] PMID: 40922085
Abstract: Genetic predisposition and environmental factors, including psychological stress, play prominent roles in driving the development and progression of colorectal neoplasms. However, the mechanisms through which chronic stress drives the progression of colorectal neoplasm remain unclear. The gut microbiota is closely linked to chronic psychological stress (chronic stress) and colorectal neoplasms. Here, we found that chronic stress significantly promoted tumor growth in patients with colorectal cancer and mouse models of colitis-associated colorectal cancer, while concurrently reducing the abundance ofAkkermansia muciniphila in fecal and tumor samples. Restoring the A. muciniphila abundance mitigated the tumor-promoting effects of chronic stress. Furthermore, we identified A. muciniphila outer membrane vesicles as key mediators of the protective effect of this microbe. In conclusion, A. muciniphila alleviates chronic stress-induced colorectal neoplasm growth by releasing outer membrane vesicles. These findings highlight a connection among chronic stress, the gut microbiota, and colorectal neoplasms, providing a theoretical foundation for therapeutic strategies aimed at managing tumor progression in patients with colorectal cancer experiencing chronic stress.
6. Engineered extracellular vesicles for targeted FGF20 delivery enhance neuroplasticity and functional recovery in ischemic stroke.
用于靶向 FGF20 递送的工程化细胞外囊泡可增强缺血性中风的神经可塑性和功能恢复。
[J Control Release] PMID: 40749848
Abstract: Stroke is the second leading cause of death and the primary cause of disability worldwide, yet effective treatments to restore neurological function remain limited. Fibroblast growth factor 20 (FGF20), a promising neurotrophic factor with demonstrated efficacy in neurological disorders, faces a critical translational barrier due to its poor blood-brain barrier (BBB) permeability. To address this limitation, we developed genetically engineered rabies virus glycoprotein (RVG)-modified extracellular vesicles loaded with FGF20 (RVG-FGF20-EVs) for targeted ischemic brain delivery. Systemic administration of RVG-FGF20-EVs in a mouse middle cerebral artery occlusion (MCAO) model significantly reduced infarct volume, enhanced neuroplasticity, and improved long-term functional recovery. Mechanistic investigations revealed that RVG-FGF20-EVs exhibit a distinct miRNA cargo profile, characterized by significant upregulation of miR-181b-5p. Dual-luciferase reporter assays confirmed phosphatase and tensin homolog (PTEN) as a direct target of miR-181b-5p. Our findings demonstrate that RVG-FGF20-EVs promote neuroplasticity and functional recovery post-stroke, mediated at least partially through the miR-181b-5p/PTEN pathway. This study represents the first application of engineered RVG-EVs for efficient FGF20 brain delivery for efficient FGF20 delivery, establishing their unique efficacy in treating ischemic stroke and providing a multifunctional platform for treating neurological disorders. Further optimization and standardization are needed to translate this promising platform into clinical applications. In conclusion, RVG-FGF20-EVs constitute a promising novel therapeutic strategy for ischemic stroke.
7. Exosomal CagA induces macrophage polarization and ferroptosis by JAK1-2/STAT1 signaling pathway in Helicobacter pylori-associated gastritis.
外泌体 CagA 通过 JAK1-2/STAT1 信号通路诱导幽门螺杆菌相关胃炎中的巨噬细胞极化和铁死亡。
[Free Radic Biol Med] PMID: 40706822
Abstract: Helicobacter pylori (H. pylori) infection is a major cause of gastric diseases, with the virulence factor CagA carried by exosomes playing a crucial role in regulating inflammation. Ferroptosis and M1 polarization are key mechanisms in promoting inflammation, yet the role of CagA in inducing macrophage ferroptosis and M1 polarization to exacerbate gastric mucosal inflammation remains unclear.In this study, CagA-positive (CagA+) and CagA-negative (CagA-) H. pylori strains were co-cultured with gastric epithelial cells, and exosomes were isolated to assess their impact on macrophage polarization and ferroptosis markers. We found that exosomal CagA induces M1 polarization and ferroptosis in macrophages by activating the JAK/STAT1 signaling pathway. The ferroptosis inhibitor SLC7A11 plays a key role in CagA-induced ferroptosis. Furthermore, exosomal CagA enhances STAT1 nuclear expression, which binds to the SLC7A11 promoter, downregulating its expression. In biopsies from CagA+ H. pylori-infected gastritis patients, increased iNOS levels and reduced SLC7A11 expression were observed. Our findings indicate that exosomal CagA promotes macrophage M1 polarization and ferroptosis through the JAK/STAT1 signaling pathway. This study provides new insights and potential therapeutic targets for H. pylori-associated gastritis.
今天的整理就到这里。希望大家可以有所收获。大家下周见！
