The present study aimed to explore the effects of key N6‑methyladenosine (m6A)‑related long non‑coding RNAs (lncRNAs) on the malignant behavior and macrophage polarization of gastric cancer cells, and their preliminary mechanisms. Gastric cancer‑related lncRNA datasets were downloaded from The Cancer Genome Atlas database, and m6A‑related differentially expressed lncRNAs (DElncRNAs) were analyzed. Subsequently, Cox regression and lasso regression analyses were used to screen the m6A‑related DElncRNAs associated with the prognosis of patients with gastric cancer. Additionally, reverse transcription‑quantitative polymerase chain reaction (qPCR) was employed to detect the expression levels of m6A‑related lncRNAs in normal gastric epithelial cells (GES‑1) and human gastric cancer cells (AGS and MKN‑45). In addition, the methylation levels of lncRNAs were measured using a methylated RNA immunoprecipitation qPCR assay kit, and the interaction between m6A‑related lncRNAs and m6A‑related proteins was observed by RNA pull‑down assay. Subsequently, m6A‑related lncRNAs and proteins were knocked down separately or simultaneously in gastric cancer cell lines. Bioinformatics analysis revealed that m6A‑related AC026691.1 was significantly associated with the prognosis of patients with gastric cancer and had a potential binding site for YT521‑B homology domain family member 2 (YTHDF2). The RNA pull‑down assay indicated that YTHDF2 not only had binding sites with AC026691.1 but could also markedly promote the degradation of m6A‑related AC026691.1. Furthermore, AC026691.1 was lowly expressed in gastric cancer cells, whereas YTHDF2 was highly expressed. Knockdown of YTHDF2 inhibited the proliferation, migration and epithelial‑mesenchymal transition of gastric cancer cells, and reduced M2 macrophage polarization. By contrast, knocking down AC026691.1 showed the opposite trend. Knockdown of YTHDF2 and AC026691.1 further confirmed the stable impact of YTHDF2 on AC026691.1. In conclusion, the degradation of AC026691.1 modified by YTHDF2‑mediated m6A may promote gastric cancer cell proliferation, migration, epithelial‑mesenchymal transition and M2 macrophage polarization.

Metastasis is the leading cause of mortality for colorectal cancer (CRC). Cancer-derived exosomes are widely recognized as the primary catalysts behind the development of pre-metastasis niche (PMN) in distal sites. However, the exact mechanism behind this process in CRC remains elusive. This study aimed to investigate the function and mechanisms underlying the role of exosomal miR-188-3p in activating hepatic stellate cells (HSCs) to develop the PMN and promote liver metastasis.

We extracted exosomes from CRC cells using ultracentrifugation. Exosomes were identified using transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Exosome uptake was assessed using fluorescence tracing, exosome PKH67 staining, and real-time quantitative PCR. The effects of CRC cell-derived exosomes on HSCs migration were evaluated using Transwell migration and wound healing assays. Key differentially expressed miRNAs were screened from the GEO database, and bioinformatics prediction along with dual-luciferase reporter assays were used to identify downstream target genes of miR-188-3p. Downstream related proteins of the target genes were detected by Western blot. In vivo, the distribution of exosomes and activation of HSCs in the liver were explored by tail vein injection of exosomes into nude mice. Further, the impact of exosomal miR-188-3p on liver metastasis was investigated using a spleen injection liver metastasis model. Finally, the expression levels of miR-188-3p in exosomes from CRC patient plasma were determined by real-time quantitative PCR, and the relationship between the expression of miR-188-3p in plasma exosomes and CRC prognosis was analyzed.

The expression level of miR-188-3p within plasma exosomes demonstrated a statistically significant increase in CRC with liver metastasis compared to those without liver metastases. We also demonstrated the transferability of miR-188-3p from CRC cells to HSCs cells via the exosomes. Exosomal miR-188-3p plays a pivotal role in orchestrating the establishment of PMN through targeting PHLPP2 to activate HSCs before tumor metastasis. Exosomal miR-188-3p was found to actively foster in vivo metastasis of CRC. Additionally, plasma exosomal miR-188-3p potentially serves as a viable blood-based biomarker for CRLM.

Exosomal miR-188-3p derived from CRC cells can promote liver metastasis by activating HSCs to form a PMN through targeting PHLPP2 to activate the AKT/mTOR pathway. These results offer a new perspective on the mechanisms driving CRLM.

Exosomes mediate cell-to-cell communication by releasing miRNAs, mRNA, etc. However, there is little research about the effects on the donor cells after miRNAs are excreted out of cells through exosomes. Here, we found that miR-378a-3p was specifically enriched in exosomes and inhibited cell proliferation, migration, invasion, and colony formation in ESCC. In addition, miR-378a-3p was sorted into exosomes through TOM1L1 and extracted mainly out of ESCC cells. Overexpression of TOM1L1 led to tumor suppressor miR-378a-3p accumulation in exosomes rather than in donor cells, promoting ESCC progression. Moreover, miR-378a-3p targets DYRK1A that directly binds to NPM1 and the phosphorylation state of NPM1 at Ser125 to suppress tumor growth. Taken together, our findings demonstrate that TOM1L1-mediated the tumor suppressor miR-378a-3p into exosomes and excreted out of cells to promote tumor progression.

Cancer metastasis is a complicated biological process that critically affects cancer progression, patient outcomes, and treatment plans. A significant step in metastasis is the formation of a pre-metastatic niche (PMN). A small subset of cells within tumors, known as cancer stem cells (CSCs), possess unique characteristics including, differentiation into different cell types within the tumor, self-renewal, and resistance to conventional therapies, that enable them to initiate tumors and drive metastasis. PMN plays an important role in preparing secondary organs for the arrival and proliferation of CSCs, thereby facilitating metastasis. CSC-derived exosomes are crucial components in the complex interplay between CSCs and the tumor microenvironment. These exosomes function as transporters of various substances that can promote cancer progression, metastasis, and modulation of pre-metastatic environments by delivering microRNA (miRNA, miR) cargo. This review aims to illustrate how exosomal miRNAs (exo-miRs) secreted by CSCs can predispose PMN and promote angiogenesis and metastasis.

Renal cell carcinoma (RCC) is an aggressive malignancy originating from the renal parenchyma, often leading to high mortality due to local invasion and distant metastasis. MicroRNAs (miRNAs) play essential roles in RCC progression. Through miRNA sequencing, we identified significant upregulation of miR-222-3p in metastatic RCC tissues. Exosomes from highly metastatic RCC cells were found to transfer miR-222-3p to low-metastatic cells, enhancing their migration and invasion. Mechanistically, miR-222-3p directly targets the 3' untranslated region (3'UTR) of the tumor-suppressor TRPS1, reducing its expression. TRPS1 downregulation releases its inhibitory effect on ZEB1, a key regulator of epithelial-mesenchymal transition (EMT), thereby promoting EMT and metastatic traits. ZEB1 further transactivates miR-222-3p, establishing a positive feedback loop. Additionally, miR-222-3p promotes a pre-metastatic niche by inducing M2 macrophage polarization, facilitating distant metastasis. These findings highlight miR-222-3p as a critical driver of RCC metastasis and suggest its potential as a diagnostic marker and therapeutic target for RCC.

Periodontitis is the most common non-communicable disease in humans. The main challenge in the treatment of periodontitis is to effectively control periodontal inflammation and promote tissue repair. Human umbilical cord mesenchymal stem cells-derived exosomes (hucMSCs-exo) have been reported to modulate inflammatory responses and promote tissue repairment mainly through miRNAs in several diseases. However, the effect of hucMSCs-exo on periodontitis remains unknown. In this study, we hypothesized that hucMSCs-exo could inhibit bone destruction in periodontitis mice.

In this study, we constructed and characterized the exo@H drug delivery platform. Lipopolysaccharide was used to construct an inflammatory microenvironment in vitro to detect MC3T3-E1 cells proliferation and bone regeneration capacity. Ligation induced to construct an experimental periodontitis mouse model. The distance of the cement-enamel junction (CEJ) to the alveolar bone crest (ABC) was measured for bone resorption evaluation. Hematoxylin-eosin (H&E) staining and Tartrate resistant acid phosphatase (TRAP) staining were used to observe periodontal tissue changes. MicroRNA (miRNA) sequencing was used to detect differential genes and for bioinformatics analysis. Real-time quantitative polymerase chain reaction (qRT-PCR). WB assay and dual luciferase assay were used to further validate the screened differentially expressed miRNAs and the targeted binding relationship with the corresponding target genes.

We found that lyophilized hucMSCs-exo promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells, and showed more significant proliferative and osteogenic differentiation abilities in combination with the hydrogel (P < 0.05). Using periodontitis mice, bone resorption evaluation revealed a significant reduction in alveolar bone resorption in the exo@H group compared to the hydrogel group (P < 0.01), and exo@H was able to reduce the inflammatory response of periodontal tissues and the number of osteoclasts on the surface of the alveolar bone compared to the hydrogel group. Moreover, 59 miRNAs were upregulated, such as let-7f-5p and miR-203-3p, which positively targeted IL-13 and Nit2, respectively.

These results suggest that exo@H provides protection against periodontitis partly by delivering miRNAs to periodontal tissue. Our results confirm the feasibility of the exo@H delivery platform we constructed and the effectiveness of its use for periodontitis treatment, and this study provides a promising approach for the treatment of periodontitis via miRNA.

Subclinical hypothyroidism (SCH) contributes to obesity, with the liver acting as a crucial metabolic regulator. Thyroid-stimulating hormone (TSH) affects systemic lipid balance, potentially linking SCH to obesity. While the direct impact of TSH on hepatic lipid metabolism has been extensively documented, its role in modulating lipid dynamics in peripheral organs through liver-mediated pathways remains insufficiently understood. This study identifies TSH-stimulated hepatocyte-derived exosomes (exosomesTSH) as key mediators in liver-adipose communication, promoting triglyceride accumulation in adipocytes via the transforming growth factor-beta 1 (TGF-β1)/adipose triglyceride lipase (ATGL) axis. ExosomesTSH enhance lipid storage in adipocytes, significantly increasing triglyceride content and lipid droplet formation while reducing lipolysis, effects that are dependent on TSH receptor (TSHR) activation in hepatocytes. In vivo, exosomesTSH induce weight gain and adipose tissue expansion, impairing glucose metabolism in both chow- and high-fat diet-fed mice. Mechanistically, exosomesTSH upregulate TGF-β1 and downregulate ATGL in adipocytes, establishing the TGF-β1/ATGL pathway as essential for exosome-mediated lipid accumulation. Further, miR-139-5p is identified as a modulator of TGF-β1 expression within this pathway, with overexpression of miR-139-5p alleviating exosomesTSH-induced lipid accumulation in adipocytes. This study elucidates a novel miR-139-5p-dependent mechanism through which TSH modulates lipid metabolism via liver-derived exosomes, highlighting the pivotal role of miR-139-5p in linking SCH to adipose lipid accumulation through the TGF-β1/ATGL signaling axis.

Gastric cancer (GC) is one of the most common gastrointestinal cancers worldwide, with consistently high morbidity and mortality rates and poor prognosis. Most patients are diagnosed at an advanced stage due to the lack of specific presentation in the early stages. Exosomes are a class of extracellular vesicles (EVs) widely found in body fluids and can release genetic material or multiple proteins to facilitate intercellular communication. In recent years, exosomal miRNAs have gained attention for their role in various cancers. These exosomal miRNAs can impact GC development and progression by targeting specific genes or influencing signaling pathways and cytokines involved in Angiogenesis, epithelial-mesenchymal transition (EMT), drug resistance, and immune regulation. They show great potential in terms of diagnosis, prognosis, and treatment of GC. Notably, the gastrointestinal tract has the largest number of macrophages, which play a significant role in GC progression. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and can influence macrophage programming through various mediators, including macrophage polarization. Macrophage polarization is involved in inflammatory responses and significantly impacts the GC process.

MCT4 is a lactate transporter associated with glycolysis, which has been found to be associated with various tumorigenesis and development processes. Gastric cancer is a malignant disease with high incidence and mortality. The role of MCT4 in the occurrence and development of gastric cancer has not been clarified.

In this study, we comprehensively utilized single-cell sequencing and external transcriptome sequencing databases to deeply analyze the mechanism of the impact of MCT4 on gastric cancer and its microenvironment. We verified the function of MCT4 in gastric cancer through in vitro cell line experiments and in vivo experiments using gastric cancer liver metastasis and subcutaneous tumor models. Meanwhile, we collected tumor and normal tissue samples from clinical gastric cancer patients and employed immunohistochemistry and multiplex immunofluorescence techniques to detect the expression and localization of relevant indicators, thereby validating the results of computer simulation analysis and providing a basis for revealing the internal relationship between MCT4 and gastric cancer.

The expression of MCT4 is upregulated in gastric cancer patients, and the upregulation is more significant than that in patients with gastric cancer metastasis. MCT4 can mediate the proliferation and migration of gastric cancer cells in vitro. MCT4 can mediate the metastasis of gastric cancer cells in vivo. Multi-omics analysis showed that the expression of MCT4 was related to the composition of the immune microenvironment, and it could mediate the emergence of the inhibitory immune microenvironment. The results of immunofluorescence and immunohistochemistry proved the robustness of the multi-omics analysis.

Our study found that MCT4 plays an important role in the occurrence and development of gastric cancer, which may mediate the occurrence of gastric cancer metastasis and shape the immunosuppressive tumor microenvironment.

Gastric cancer liver metastasis (GCLM) refers to the process of cancer cells from the stomach spreading to the liver, which is an important sign of the deterioration of gastric cancer (GC) and has a profound influence on the treatment and prognosis of patients. Once GC has liver metastasis, the treatment becomes more complex and challenging, which seriously affects the survival rate of patients with GC. Therefore, studying the mechanism and treatment of GCLM is extremely necessary. At present, the continuous research on GCLM has revealed that the mechanism of its occurrence and development involves the comprehensive effect of multiple targets and links. Traditional Chinese medicine (TCM) has the advantages of wide sources, excellent efficacy, and small toxicity and side effects, which have become the focus of current antitumor research. TCM, Chinese medicine monomers, or TCM compounds can inhibit the growth and metastasis of GC. In recent years, Chinese medicine has made substantial achievements in experimental research on the intervention of GCLM. This article reviews the progress of its intervention mechanism.

Liver metastasis is a leading cause of mortality from malignant tumors and significantly impairs the efficacy of therapeutic interventions. In recent years, both preclinical and clinical research have made significant progress in understanding the molecular mechanisms and therapeutic strategies of liver metastasis. Metastatic tumor cells from different primary sites undergo highly similar biological processes, ultimately achieving ectopic colonization and growth in the liver. In this review, we begin by introducing the inherent metastatic-friendly features of the liver. We then explore the panorama of liver metastasis and conclude the three continuous, yet distinct phases based on the liver's response to metastasis. This includes metastatic sensing stage, metastatic stress stage, and metastasis support stage. We discuss the intricate interactions between metastatic tumor cells and various resident and recruited cells. In addition, we emphasize the critical role of spatial remodeling of immune cells in liver metastasis. Finally, we review the recent advancements and the challenges faced in the clinical management of liver metastasis. Future precise antimetastatic treatments should fully consider individual heterogeneity and implement different targeted interventions based on stages of liver metastasis.

Gastric cancer is a common and highly invasive type of malignant tumor, the pathogenesis of which remains unclarified. However, exosomes are now known to play important roles in gastric cancer development and treatment. Cells use exosomes for the packaging and transportation of a variety of bioactive molecules, such as proteins, double-stranded DNA, and micro-ribonucleic acids, to other sites. Exosome-specific membrane structures and exosomal contents are widely involved in processes that facilitate material exchange and intercellular communication between gastric cancer cells. They help in forming a pre-metastatic microenvironment, promoting the proliferation and apoptosis of gastric cancer cells, and driving invasion, metastasis, and resistance to anti-tumor drugs. In this review, we aimed to summarize the findings of research articles indexed in the PubMed, Web of Science, and Embase databases and published up to May 31, 2024, on the role of exosomes in the pathogenesis of gastric cancer and their potential clinical applications in its treatment. Thus, research on exosomes may lead to breakthroughs in the early diagnosis of gastric cancer and identification of novel treatments.

Colorectal cancer liver metastases (CRLM) are the primary cause of mortality in colorectal cancer (CRC) patients, highlighting the importance of understanding the underlying mechanisms. The tumor microenvironment (TME) and its interaction with tumor cells play a crucial role in CRLM progression. Notably, the stability and peak levels of tumor-derived exosomal miRNAs facilitate intercellular communication in the TME. Hepatic stellate cells (HSCs), key liver mesenchymal cells, constitute about 33% of the liver's nonsolid cell population and exhibit plasticity. However, the specific role of tumor-derived exosomal miRNAs in the crosstalk between HSCs and tumor cells during the CRLM process remains unclear. We studied CRC-secreted exosomal miR-1246 and its impact on HSCs, as well as its effects on CRC cell proliferation and metastasis. Our findings demonstrate that CRC-secreted exosomal miR-1246 can be internalized by HSCs, leading to their activation and facilitating the metastatic potential of CRC cells. Mechanistically, exosomal miR-1246 targets INSIG1, resulting in SREBP2 nucleation and cholesterol metabolism alterations. This accumulation of free cholesterol (FC) regulates the TLR4/NF-κB/TGF-β pathway, promoting HSC activation. Activated HSCs, in turn, enhance liver metastasis of CRC cells through the TNFSF13/TNFRSF13B axis. Our study reveals the role of CRC-secreted exosomal miR-1246 in triggering HSC activation and reprogramming the TME, ultimately facilitating liver metastasis in CRC patients. Exosomal miR-1246 could serve as a potential non-invasive biomarker for predicting colorectal cancer liver metastasis, enhancing our understanding of CRC-associated liver metastases.

Metastasis is a hallmark of advanced cancer, and the liver is a common site for secondary metastasis of many tumor cells, including colorectal, pancreatic, gastric, and prostate cancers. Macrophages in the tumor microenvironment (TME) promote tumor cell metastasis through various mechanisms, including angiogenesis and immunosuppression, and play a unique role in the development of liver metastasis. Macrophages are affected by a variety of factors. Under conditions of hypoxia and increased acidity in the TME, more factors are now found to promote the polarization of macrophages to the M2 type, including exosomes and amino acids. M2-type macrophages promote tumor cell angiogenesis through a variety of mechanisms, including the secretion of factors such as VEGF, IL-1β, and TGF-β1. M2-type macrophages are subjected to multiple regulatory mechanisms. They also interact with various cells within the tumor microenvironment to co-regulate certain conditions, including the creation of an immunosuppressive microenvironment. This interaction promotes tumor cell metastasis, drug resistance, and immune escape. Based on the advent of single-cell sequencing technology, further insights into macrophage subpopulations in the tumor microenvironment may help in exploring new therapeutic targets in the future. In this paper, we will focus on how macrophages affect the TME, how tumor cells and macrophages as well as other immune cells interact with each other, and further investigate the mechanisms involved in liver metastasis of tumor cells and their potential as therapeutic targets.

Gastric cancer (GC) is a common and frequent malignant cancer of the digestive system with a poor prognosis. In addition to common therapies such as surgical resection and chemotherapy, novel biological interventions are quite valuable for research. Exosomes are extracellular vesicles (EVs) that originate from various cell types and contain proteins, RNA, DNA, and other components that transmit biological signals and mediate intercellular communication. Numerous studies have shown that exosomes shape the tumor microenvironment (TME) by affecting hypoxia, inflammation, immunity, metabolism, and interstitial changes in the tumor, playing a crucial role in the development and metastasis of GC. This article reviews the important role of exosomes in the TME of GC and explores their potential clinical applications in GC treatment.

Exosomes are membrane-bound extracellular vesicles that play a role in exchanging biological products across membranes and serve as intermediaries in intercellular communication to maintain normal homeostasis. Numerous molecules, including lipids, proteins, and nucleic acids are enclosed in exosomes. Exosomes are constantly released into the extracellular environment and exhibit distinct characteristics based on the secreted cells that produce them. Exosome-mediated cell-to-cell communication has reportedly been shown to affect multiple cancer hallmarks, such as immune response modulation, pre-metastatic niche formation, angiogenesis, stromal cell reprogramming, extracellular matrix architecture remodeling, or even drug resistance, and eventually the development and metastasis of cancer cells. Exosomes can be used as therapeutic targets and possible diagnostic biomarkers by selectively loading oncogenic molecules into them. We highlight the important roles that exosomes play in cancer development in this review, which may lead to the development of fresh approaches for future clinical uses.

In this review, we explore the application of next-generation sequencing in liver cancer research, highlighting its potential in modern oncology. Liver cancer, particularly hepatocellular carcinoma, is driven by a complex interplay of genetic, epigenetic, and environmental factors. Key genetic alterations, such as mutations in TERT, TP53, and CTNNB1, alongside epigenetic modifications such as DNA methylation and histone remodeling, disrupt regulatory pathways and promote tumorigenesis. Environmental factors, including viral infections, alcohol consumption, and metabolic disorders such as nonalcoholic fatty liver disease, enhance hepatocarcinogenesis. The tumor microenvironment plays a pivotal role in liver cancer progression and therapy resistance, with immune cell infiltration, fibrosis, and angiogenesis supporting cancer cell survival. Advances in immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies have shown potential, but the unique immunosuppressive milieu in liver cancer presents challenges. Dysregulation in pathways such as Wnt/β-catenin underscores the need for targeted therapeutic strategies. Next-generation sequencing is accelerating the identification of genetic and epigenetic alterations, enabling more precise diagnosis and personalized treatment plans. A deeper understanding of these molecular mechanisms is essential for advancing early detection and developing effective therapies against liver cancer.

Peak oxygen consumption during exercise (VO 2 peak), is a direct measure of cardiorespiratory fitness (CF), a key indicator of physical function and overall health. However, the molecular changes that underpin VO 2 peak variation are not clear. Our objective is to understand the miRNA signatures that relate to VO 2 peak variation, which could provide insights to novel mechanisms that contribute to low VO 2 peak.

We used small RNA sequencing to analyze serum samples from 72 participants (70-79 yrs old, 53% female) of the Study of Muscle, Mobility and Aging (SOMMA). We analyzed samples from individuals with low or high VO 2 peak (N=18/group) as well as samples from 36 randomly selected participants spanning the entire spectrum of VO 2 peak. We used LIMMA analysis package for regression analysis and to identify differentially expressed miRNAs. We used receiver operating characteristic curve analysis to evaluate the Area Under the Curve (AUC) and sensitivity and specificity rates.

We identified 1,055 miRNAs expressed in all serum samples. Expression of 65 miRNAs differed between participants with low and high VO 2 peak (p < 0.05). After p-value adjustment, expression of 5 miRNAs (miR-1301-3p, -431-5p, -501-5p, -519a-3p, and -18a-3p) remained significantly different (FDR = 0.05). The five miRNAs had AUC ranging from 0.77 to 0.84. The optimal sensitivity and specificity ranged from 70 to 80% and 80 to 90%, respectively. After adjustment for age and sex covariates, 46 miRNAs significantly correlated with VO 2 peak (p < 0.05) and miR-519a-3p remained significant based on adjusted of p-values.

We identified a miRNA signature of VO 2 peak in older individuals that might provide insights to novel mechanisms that drive low VO 2 peak. Future studies will validate the findings in a larger, longitudinal study cohort.

Liver metastasis is the major cause of death in colorectal cancer (CRC) due to the lack of effective treatment. To explore novel drivers of CRC liver metastasis, the transcriptomes of primary paracancerous, colorectal tumors and metastases from human patients are profiled. It is found that SLIT- and NTRK-like family member 4 (SLITRK4) is the top upregulated gene in liver metastases and is associated with worse overall survival of CRC patients. Multiple in vitro and in vivo models suggested SLITRK4 promoted CRC tumorigenesis, invasion, migration, and angiogenesis, and inhibition of it restrained CRC tumor growth and liver metastasis with a more profound effect on the tumor microenvironment (TME). Mechanistically, SLITRK4 overexpression significantly activated the PI3K/AKT/NFκB pathway, regulated extracellular matrix organization, and multiple cytokines expression. Furthermore, the results from coculture models and single-cell RNA sequencing analyses suggested SLITRK4 promoted tumor-associated macrophages (TAMs) infiltration and polarization. In addition, macrophage depletion significantly inhibited SLITRK4-induced liver metastasis in CRC. Finally, pharmacological inhibition of SLITRK4 by using lipid-polymer hybrid nanoparticles (NPs) for systemic siRNA delivery can effectively inhibit CRC liver metastasis. Taken together, these results pinpoint that SLITRK4 regulates CRC tumorigenesis and liver metastasis, and siRNA delivering NPs agents validate the therapeutic potential of targeting SLITRK4 in CRC.

Cancer-associated fibroblasts (CAFs) can interact with macrophages in the tumor microenvironment by secreting extracellular vesicles (EVs), thereby affecting tumor progression. However, the mechanisms of CAF-secreted EVs in gastric cancer (GC) remain not well understood. Here, we investigated the effect of CAF-EVs on macrophage polarization in GC and the underlying mechanisms. Macrophage polarization was evaluated using flow cytometry and quantitative real-time polymerase chain reaction. GC cell proliferation was determined using cell counting kit-8, EdU, and colony formation assays. The molecular mechanism was explored using microarray analysis, dual-luciferase reporter assay, and RNA pull-down analysis. The results showed that CAFs secreted EVs that inhibit macrophage M1 polarization and promote M2 polarization. Moreover, miR-4253 expression was increased in CAF-EVs, and inhibition of miR-4253 reversed the macrophage polarization induced by EVs. IL6R was identified as the target of miR-4253. Additionally, macrophages treated with EVs that encapsulated miR-4253 promote GC cell proliferation. In conclusion, CAF-secreted EVs packaging miR-4253 facilitate macrophage polarization from M1 to M2 phenotype by targeting IL6R, thereby accelerating GC cell proliferation. The findings suggest that EV-encapsulated miR-4253 may be a promising therapeutic target of GC.

Tumor-derived exosomes are highly correlated with tumor progression and angiogenesis. This study was designed to probe the role of tumor-derived exosomal miR-1247-3p in mediating the angiogenesis in bladder cancer. Exosomes isolation from the culture medium of normal or bladder cancer cell lines was performed using a differential centrifugation method. miR-1247-3p expression in exosomes and cells was detected by quantitative real-time PCR (qRT-PCR). The effect of exosomes on the angiogenesis of human umbilical vein endothelial cells (HUVECs) was assessed using cell counting kit-8 (CCK-8), transwell and tube formation assays. The interaction between miR-1247-3p and forkhead box protein O1 (FOXO1) was studied using luciferase reporter and RNA pull down assays. Exosomes were successfully isolated from T24, UM-UC-3, and SV-HUC-1 cells, as confirmed by corresponding identifications. Functional experiments revealed that exosomes derived from T24 and UM-UC-3 cells significantly enhanced the abilities of proliferation, migration, angiogenesis, and vascular endothelial-derived growth factor (VEGF) secretion in HUVECs. miR-1247-3p was highly expressed in exosomes derived from T24 and UM-UC-3 cells, and exosomes derived from miR-1247-3p inhibitor-transfected cells reduced HUVEC viability, migration, tube formation, and VEGF level. FOXO1 was confirmed as a direct target of miR-1247-3p. Rescue assays suggested that the effect of miR-1247-3p inhibition on the viability, migration, and angiogenesis of HUVECs was partly abrogated by the knockdown of FOXO1. Our data suggest that miR-1247-3p is up-regulated in tumor-derived exosomes, thereby inhibiting FOXO1 expression and facilitating angiogenesis in bladder cancer.

The levels of M2 macrophages are significantly associated with the prognosis of hepatocellular carcinoma (HCC), however, current detection methods in clinical settings remain challenging. Our study aims to develop a weakly supervised artificial intelligence model using globally labeled histological images, to predict M2 macrophage levels and forecast the prognosis of HCC patients by integrating clinical features.

CIBERSORTx was used to calculate M2 macrophage abundance. We developed a slide-level, weakly-supervised clustering method for Whole Slide Images (WSIs) by integrating Masked Autoencoders (MAE) with ResNet-32t to predict M2 macrophage abundance.

We developed an MAE-ResNet model to predict M2 macrophage levels using WSIs. In the testing dataset, the area under the curve (AUC) (95% CI) was 0.73 (0.59-0.87). We constructed a Cox regression model showing that the predicted probabilities of M2 macrophage abundance were negatively associated with the prognosis of HCC (HR=1.89, p=0.031). Furthermore, we incorporated clinical data, screened variables using Lasso regression, and built the comprehensive prediction model that better predicted prognosis. (HR=2.359, p=0.001).

Our models effectively predicted M2 macrophage levels and HCC prognosis. The findings suggest that our models offer a novel method for determining biomarker levels and forecasting prognosis, eliminating additional clinical tests, thereby delivering substantial clinical benefits.

Colorectal cancer is a common malignant tumor, whose growth and metastasis are influenced by numerous factors. MicroRNAs have garnered increasing attention in recent years due to their involvement in tumor development. Exosomes are involved in intercellular signaling and influence tumor development by promoting tumor cell proliferation and metastasis through activation of angiogenesis and other mechanisms. This study aimed to investigate how the exosomes containing miR-320d from colorectal cancer (CRC) cells promote colorectal cancer metastasis by regulating angiogenesis. CRC-derived exosomes containing miR-320d can be transferred to vascular endothelial cells, facilitating their proliferation, invasion, migration, and angiogenesis. By targeting GNAI1, miR-320d in these exosomes reduces GNAI1 levels in endothelial cells, causing more JAK2/STAT3 activation and VEGFA production. This ultimately enhances the migration and angiogenic capacity of vascular endothelial cells. Moreover, CRC patients with high levels of miR-320d in their blood respond better to treatment with bevacizumab. In vivo experiments further proved the role of miR-320d from CRC exosomes in increasing tumor size, blood vessel formation, and the spread of cancer to the liver. In this study, we have demonstrated that exosomal miR-320d promotes cancer cell metastasis and enhances angiogenesis by downregulating GNAI1 expression and enhancing JAK2/STAT3.

The progression of hepatoma is heavily influenced by the microenvironment. Tumor-associated macrophages (TAMs) are considered to play a critical role in the tumor microenvironment (TME) and increase the aggressiveness of hepatoma. The activation of hepatic stellate cells (HSCs) is involved in hepatoma progression, and accumulating evidence demonstrates a change in microRNA (miRNA) expression during HSC activation. Therefore, the potential roles of HSCs-related miRNAs in macrophage differentiation and hepatoma progression deserve to be explored. The present study aimed to investigate the effects of miRNAs carried by small extracellular vesicles (sEVs) released by activated HSCs on hepatoma progression. The results indicated that miR-27a-3p was significantly upregulated in cells and corresponding sEVs during the activation of primary rat HSCs and human HSC line-LX2 cells. Furthermore, miR-27a-3p contributed to the proliferation and migration of hepatoma cells and promoted M2 polarization of macrophage. HSC-sEVs overexpressing miR-27a-3p can directly facilitate tumor progression and modulate macrophage polarization, indirectly contributing to hepatoma progression. Finally, Sprouty2 (SPRY2) was verified to be the target gene of miR-27a-3p. In conclusion, activated HSC-derived sEVs with high levels of miR-27a-3p might induce M2 macrophage polarization and promote hepatoma progression, providing new insights into the mechanism of hepatoma progression.

Stomach cancer is considered the fifth most common cancer worldwide. This study utilized bibliometric analysis to construct a visualization map of the relationship between stomach cancer and exosomes, aiming to reveal research trends and emerging themes, and provide direction for future research.

Retrieve relevant literature on gastric cancer exosomes in the Web of Science Core Collection (WoSCC) over the past 25 years according to search criteria, and conduct bibliometric and visualization analysis using bibliometric software VOSviewer and CiteSpace.

This study included a total of 727 articles, with an overall increasing trend in annual publication output. There were 68 countries involved, with China having the largest number of publications followed by the United States. A total of 957 research institutions were involved, with most of the top 10 institutions in terms of publication output being universities in China. The top 5 journals are Molecular Cancer, Cell death & disease, Cancers, International journal of molecular sciences, and Frontiers in oncology. A total of 4529 authors were involved, with 5 authors having a publication output of no less than 13 articles. A total of 35516 references were cited, with a total number of citations. The top publication is "Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells".

Over the past 25 years, researchers have been dedicated to studying the field of exosomes related to gastric cancer, and research in this area is currently progressing steadily. Based on previous studies, exosomes in gastric adenocarcinoma serve as biomarkers, potential therapeutic targets, and post-resistance treatment, which represents current hotspots and emerging frontiers in research.

From their early genesis, tumour cells integrate with the surrounding normal cells to form an abnormal structure that is tightly integrated with the host organism via blood and lymphatic vessels and even neural associations. Using these connections, emerging cancers send a plethora of mediators that efficiently perturb the entire organism and induce changes in distant tissues. These perturbations serendipitously favour early metastatic establishment by promoting a more favourable tissue environment (niche) that supports the persistence of disseminated tumour cells within a foreign tissue. Because the establishment of early metastatic niches represents a key limiting step for metastasis, the creation of a more suitable pre-conditioned tissue strongly enhances metastatic success. In this Review, we provide an updated view of the mechanisms and mediators of primary tumours described so far that induce a pro-metastatic conditioning of distant organs, which favours early metastatic niche formation. We reflect on the nature of cancer-induced systemic conditioning, considering that non-cancer-dependent perturbations of tissue homeostasis are also able to trigger pro-metastatic conditioning. We argue that a more holistic view of the processes catalysing metastatic progression is needed to identify preventive or therapeutic opportunities.

Silicosis is one of the most prevalent and fatal occupational diseases worldwide, with unsatisfactory clinical outcomes. This study aimed to investigate the therapeutic effect and related molecular mechanisms of how mesenchymal stem cell (MSC)-secreted exosomes alleviate SiO2-induced pulmonary fibrosis. miR-99a-5p was significantly downregulated in silicosis models via high-throughput miRNA screening, and was overlapped with miRNAs in exosomes from MSCs. miR-99a-5p was significantly downregulated in the lung of a mice silicosis model and in TGFβ1-induced NIH-3T3 cells. In contrast, fibroblast growth factor receptor 3 (FGFR3), a direct target gene of miR-99a-5p, was upregulated in vitro and in vivo. Furthermore, we demonstrated that MSC-derived exosomes deliver enriched miR-99a-5p to target cells and inhibit TGF-β1-induced fibroblast transdifferentiation to reduce collagen protein production. Similarly, in a silicosis mouse model, MSC-derived exosome treatment through the tail veins of the mice counteracted the upregulation of fibrosis-related proteins and collagen deposition in the lung of the mice. By constructing exosomal therapeutic cell models with different miR-99a expressions, we further demonstrated that miR-99a-5p might attenuate pulmonary fibrosis by regulating target protein FGFR3 and downstream mitogen-activated protein kinase (MAPK) signalling pathways. Our study demonstrated that MSC-derived exosomes ameliorate SiO2-induced pulmonary fibrosis by inhibiting fibroblast transdifferentiation and represent an attractive method of pulmonary fibrosis treatment.

Liver metastases are commonly detected in the advanced stages of various malignant tumors, representing a significant clinical challenge. Throughout the process of liver metastases formation, immune cells play a pivotal role, particularly in the pre-metastatic and metastatic niches within the liver. Immune cells establish extensive and intricate interactions with tumor cells and other components in the liver, collectively promoting and sustaining the growth of liver metastases. Despite the limited efficacy of existing therapeutic modalities against some advanced liver metastases, novel immune-based treatment approaches are continuously being explored and validated. Building on the systematic elucidation of the immunosuppressive characteristics of liver metastases, we explored the potential of novel immunotherapies applicable to patients with liver metastases from multiple dimensions.

Angiogenesis is essential for repairing critical-sized bone defects. Although adipose-derived stem cell (ADSC)-derived exosomes have been shown to enhance the angiogenesis of endothelial progenitor cells (EPCs), the underlying mechanisms remain unclear. This study aims to explore the effects and mechanisms of ADSC-derived exosomes in enhancing bone repair by promoting EPC angiogenesis.

Transmission electron microscopy, nanoparticle tracking analysis, and Dil reagent kit were employed to identify ADSC-derived exosomes and their internalization by EPCs. Micro-CT analysis, H&E staining, and Masson staining were used to assess bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N), as well as the pathological changes and fibrosis at defect sites. Cell viability, migration, invasion, and tube formation of EPCs were evaluated using CCK-8, wound healing, Transwell, and tube formation assays. Immunohistochemical staining, RT-PCR, and Western blotting were utilized to measure the gene and protein expression of markers such as CD31, VEGFA, OCN, RUNX2, NOTCH1, and DLL4. Gene sequencing and bioinformatics analyses were conducted to identify the most highly expressed miRNA in exosomes, while miRDB and dual-luciferase reporter assays were used to explore the interaction between miR-21-5p and NOTCH1.

The ADSC-derived exosomes, averaging 126 nm in diameter, were internalized by EPCs. In vivo, these exosomes promoted new bone formation, increased BMD, BV/TV, Tb.Th, and Tb.N, reduced pathological damage to cranial defect tissues, enhanced vascular and bone tissue regeneration, and upregulated OCN and RUNX2 expression. In vitro, ADSC-derived exosomes enhanced EPC viability, migration, invasion, and tube formation. Both in vivo and in vitro experiments demonstrated that ADSC-derived exosomes upregulated CD31 and VEGFA expression. miR-21-5p, the most highly expressed miRNA in ADSC-derived exosomes, was found to target NOTCH1. Overexpression of miR-21-5p in these exosomes facilitated EPC migration, tube formation, and VEGFA expression while downregulating NOTCH1 and DLL4 expression. Inhibition of miR-21-5p produced opposite effects on EPCs.

These findings indicate that miR-21-5p in ADSC-derived exosomes promotes angiogenesis in EPCs to accelerate bone repair by targeting the NOTCH1/DLL4/VEGFA signaling pathway, offering a potential therapeutic strategy for bone defect treatment.

Distant metastases and drug resistance account for poor survival of patients with gastrointestinal (GI) malignancies such as gastric cancer, pancreatic cancer, and colorectal cancer. GI cancers most commonly metastasize to the liver, which provides a unique immunosuppressive tumour microenvironment to support the development of a premetastatic niche for tumor cell colonization and metastatic outgrowth. Metastatic tumors often exhibit greater resistance to drugs than primary tumors, posing extra challenges in treatment. The liver metastases and drug resistance of GI cancers are regulated by complex, intertwined, and tumor-dependent cellular and molecular mechanisms that influence tumor cell behavior (e.g. epithelial-to-mesenchymal transition, or EMT), tumor microenvironment (TME) (e.g. the extracellular matrix, cancer-associated fibroblasts, and tumor-infiltrating immune cells), tumor cell-TME interactions (e.g. through cytokines and exosomes), liver microenvironment (e.g. hepatic stellate cells and macrophages), and the route and mechanism of tumor cell dissemination (e.g. circulating tumor cells). This review provides an overview of recent advances in the research on cellular and molecular mechanisms that regulate liver metastases and drug resistance of GI cancers. We also discuss recent advances in the development of mechanism-based therapy for these GI cancers. Targeting these cellular and molecular mechanisms, either alone or in combination, may potentially provide novel approaches to treat metastatic GI malignancies.

The permeability of blood vessels plays a crucial role in the spread of cancer cells, facilitating their metastasis at distant sites. Small extracellular vesicles (sEVs) are known to contribute to the metastasis of various cancers by crossing the blood vessel wall. However, the role of abnormal glycoconjugates on sEVs in tumor blood vessels remains unclear. Our study found elevated levels of fucosyltransferase VII (FUT7) and its product sialyl Lewis X (sLeX) in muscle-invasive bladder cancer (BLCA), with high levels of sLeX promoting the growth and invasion of BLCA cells. Further investigation revealed that sLeX was enriched in sEVs derived from BLCA. sLeX-decorated sEVs increased blood vessel permeability by disrupting the tight junctions of human umbilical vein endothelial cells (HUVECs). Using the glycoproteomics approach, we identified integrin α3 (ITGA3) as a sLeX-bearing glycoprotein in BLCA cells and their sEVs. Mechanically, sLeX modification stabilized ITGA3 by preventing its degradation in lysosomes. sEVs carrying sLeX-modified ITGA3 can be effectively internalized by HUVECs, leading to a decrease in the expression of tight junction protein. Conversely, silencing ITGA3 in sLeX-decorated sEVs restored tight junction proteins and reduced blood vessel permeability by inhibiting the MAPK pathway. Moreover, sLeX-modification of ITGA3 at Asn 265 in HUVECs promoted occludin dephosphorylation at Ser/Thr residues, followed by inducing its importin α1-mediated nuclear translocation, which resulted in the disruption of tight junctions. Our findings suggest a potential strategy for disrupting the formation of a metastatic microenvironment and preventing the spread of malignant bladder cancer.

Colon cancer ranks second in overall cancer-related deaths and poses a serious risk to human life and health. In recent years, exosomes are believed to play an important and significant role in cancer, especially tumor-derived exosomes (TDEs). Previous studies have highlighted the pivotal role of exosomes in tumor development, owing to their ability to mediate communication between tumor cells and macrophages, induce macrophage M2 polarization, and facilitate the progression of tumorigenesis. In this study, we revealed that colon cancer-derived exosomes promoted M2-like macrophage polarization. Moreover, exosome-induced M2-like macrophages, in turn, promoted the proliferation, migration, and invasion abilities of colon cancer cells. Specifically, CT26- and HCT116-derived exosomes led to the activation of AKT, ERK, and STAT3/6 signaling pathways in THP-1(Mφ) cells. Furthermore, our findings showed that colon cancer-derived exosomes secreted lncXIST to sponge miR-17-5p, which, in turn, promoted the expression of PDGFRA, a common gene found in all three signaling pathways, to facilitate M2-like macrophage polarization. Dual-luciferase reporter assays confirmed the binding relationship between lncXIST and miR-17-5p, as well as miR-17-5p and PDGFRA. Collectively, our results highlight the novel role of lncXIST in facilitating macrophage polarization by sponging miR-17-5p and regulating PDGFRA expression.

In recent years, cancer, especially primary liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma), has posed a serious threat to human health. In the field of liver cancer, exosomes play an important role in liver cancer initiation, metastasis and interaction with the tumor microenvironment. Exosomes are a class of nanoscale extracellular vesicles (EVs)secreted by most cells and rich in bioactive molecules, including RNA, proteins and lipids, that mediate intercellular communication during physiological and pathological processes. This review reviews the multiple roles of exosomes in liver cancer, including the initiation, progression, and metastasis of liver cancer, as well as their effects on angiogenesis, epithelial-mesenchymal transformation (EMT), immune evasion, and drug resistance. Exosomes have great potential as biomarkers for liver cancer diagnosis and prognosis because they carry specific molecular markers that facilitate early detection and evaluation of treatment outcomes. In addition, exosomes, as a new type of drug delivery vector, have unique advantages in the targeted therapy of liver cancer and provide a new strategy for the treatment of liver cancer. The challenges and prospects of exosome-based immunotherapy in the treatment of liver cancer were also discussed. However, challenges such as the standardization of isolation techniques and the scalability of therapeutic applications remain significant hurdles.

Exosomes (EXO) play crucial roles in intercellular communication and glioma microenvironment modulation. Tumor-associated macrophages are more likely to become M2-like type macrophages in the immunosuppressive microenvironment. Here, we aimed to investigate the effects and molecular mechanisms of hypoxic glioma-derived exosomes mediated M2-like macrophage polarization.

Highly expressed miRNAs in exosomes derived from glioma cells cultured under hypoxia condition compared to normoxic condition were identified through microRNA sequencing. The polarization status of macrophages was determined using qRT-PCR, Western blotting, flow cytometry, and immunohistochemistry. By using RNA-seq, we aimed to identify the downstream target genes regulated by miR-25-3p in macrophages and investigate the mechanistic pathways through which it exerts its effects. The proliferation and migration capabilities of glioma cells were assessed through EdU, Transwell assays, and in vivo experiments.

We found that miR-25-3p was upregulated in the exosomes derived from hypoxic glioma cells and can be transferred to the macrophage. In macrophages, miR-25-3p downregulates the expression of PHLPP2, thereby activating the PI3K-AKT-mTOR signaling pathway, ultimately leading to macrophage M2 polarization. As part of a feedback loop, M2-polarized macrophages can, in turn, promote malignant glioma progression.

Our study reveals that miR-25-3p from hypoxic glioma cells is delivered to macrophages via exosomes as a mediator, promoting M2 polarization of macrophages through the miR-25-3p/PHLPP2/PI3K-AKT signaling pathway. This study suggests that targeted interventions to modulate miR-25-3p expression, transmission, or inhibition of PI3K-AKT pathway activation can disrupt the immune-suppressive microenvironment, providing a novel approach for immunotherapy in gliomas.

Extracellular vesicles (EVs) facilitate cell-cell interactions in the tumour microenvironment. However, standard and efficient methods to isolate tumour tissue-derived EVs are lacking, and their biological functions remain elusive.

To determine the optimal method for isolating tissue-derived EVs, we compared the characterization and concentration of EVs obtained by three previously reported methods using transmission electron microscopy, nanoparticle tracking analysis, and nanoflow analysis (Nanoflow). Additionally, the differential content of small RNAs, especially tsRNAs, between hepatocellular carcinoma (HCC) and adjacent normal liver tissues (ANLTs)-derived EVs was identified using Arraystar small RNA microarray. The targets of miRNAs and tsRNAs were predicted, and downstream functional analysis was conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, non-negative matrix factorization and survival prediction analysis.

A differential centrifugation-based protocol without cell cultivation (NC protocol) yielded higher EV particles and higher levels of CD9+ and CD63+ EVs compared with other isolation protocols. Interestingly, the NC protocol was also effective for isolating frozen tissue-derived EVs that were indistinguishable from fresh tissue. HCC tissues showed significantly higher EV numbers compared with ANLTs. Furthermore, we identified different types of small RNAs in HCC tissue-derived EVs, forming a unique multidimensional intercellular communication landscape that can differentiate between HCC and ANLTs. ROC analysis further showed that the combination of the top 10 upregulated small RNAs achieved better diagnostic performance (AUC = .950 [.895-1.000]). Importantly, most tsRNAs in HCC tissue-derived EVs were downregulated and mitochondria-derived, mainly involving in lipid-related metabolic reprogramming.

The NC protocol was optimal for isolating EVs from HCC, especially from frozen tissues. Our study emphasized the different roles of small-RNA in regulating the HCC ecosystem, providing insights into HCC progression and potential therapeutic targets.

A diverse range of gastrointestinal tract disorders are called gastrointestinal (GI) malignancies. The transformation of normal cells into precursor cells, precursor cells into premalignant cells, and premalignant cells into cancerous cells is facilitated by the interaction of many modifiable and non-modifiable risk factors. Developing relevant therapy alternatives based on a better knowledge of the illness's aetiology is essential to enhance patient outcomes. The exosome is crucial in regulating intercellular interaction because it may send molecular signals to nearby or distant cells. Exosomes produced from cancer can introduce a variety of chemicals and vast concentrations of microRNA (miRNA) into the tumour microenvironment. These miRNAs significantly impact immunological evasion, metastasis, apoptosis resistance, and cell growth. Exosomal miRNAs, or exosomal miRNAs, are essential for controlling cancer resistance to apoptosis, according to mounting data. Exosomal miRNAs function as an interaction hub between cancerous cells and the milieu around them, regulating gene expression and various signalling pathways. Our research examines the regulatory function of exosomal miRNAs in mediating interactions between cancer cells and the stromal and immunological cells that make up the surrounding milieu.

Distant metastasis is a primary cause of mortality and contributes to poor surgical outcomes in cancer patients. Before the development of organ-specific metastasis, the formation of a pre-metastatic niche is pivotal in promoting the spread of cancer cells. This review delves into the intricate landscape of the pre-metastatic niche, focusing on the roles of tumor-derived secreted factors, extracellular vesicles, and circulating tumor cells in shaping the metastatic niche. The discussion encompasses cellular elements such as macrophages, neutrophils, bone marrow-derived suppressive cells, and T/B cells, in addition to molecular factors like secreted substances from tumors and extracellular vesicles, within the framework of pre-metastatic niche formation. Insights into the temporal mechanisms of pre-metastatic niche formation such as epithelial-mesenchymal transition, immunosuppression, extracellular matrix remodeling, metabolic reprogramming, vascular permeability and angiogenesis are provided. Furthermore, the landscape of pre-metastatic niche in different metastatic organs like lymph nodes, lungs, liver, brain, and bones is elucidated. Therapeutic approaches targeting the cellular and molecular components of pre-metastatic niche, as well as interventions targeting signaling pathways such as the TGF-β, VEGF, and MET pathways, are highlighted. This review aims to enhance our understanding of pre-metastatic niche dynamics and provide insights for developing effective therapeutic strategies to combat tumor metastasis.

Immunity is a critical self-defense mechanism of the human body, wherein immune cells and immune molecules play a crucial role. Extracellular vesicles (EVs), derived from immune cells or other cells, play a significant role in tumors, autoimmune diseases and other immune-related disorders by serving as carriers and facilitating intercellular communication through the transfer of cargoes. Numerous studies have revealed that EVs can exacerbate disease development by modulating immune responses. Therefore, this paper focuses on the effects of EVs on the number, activity and function of different types of immune cells and the release of immune molecules (such as cytokines, antigens, antibodies, etc) in various diseases, as well as the roles of EVs associated with different types of immune cells in various diseases. We aim to provide a comprehensive review of the negative effects that EVs play in the immune system to provide more ideas and strategies for the management of clinical immune diseases.