Testicular sex cord stromal tumor (TSCST) is a rare testicular tumor with unknown molecular mechanisms, tumor microenvironment (TME) and limited therapeutic options. To define the molecular mechanism and potential targets of TSCST, we combined single-cell RNA sequencing with single-cell nuclear RNA sequencing along with spatial transcriptomics from different TSCST tumor regions. This revealed significantly low expression of immune cell genes in tumor areas, indicating an immune-cold tumor environment and a critical epithelial-mesenchymal transition program during tumorigenesis and disease progression. Also, the study identified high expression levels of the androgen receptor (AR) and related genes in tumor cells, suggesting AR inhibitors as potential therapeutic targets. Furthermore, we identified spatial intra-tumoral heterogeneity, with high senescent characteristics. Finally, the study reports that tumor cells might interact with macrophages, promoting M2 polarization through the APP-CD74 ligand-receptor pair, which has promising therapeutic prospects for this disease. Our data provide comprehensive insights into TSCST, including its cold TME, cellular origins, spatial niches, and cell-cell interactions, highlighting that targeting AR signaling might be a potential therapeutic strategy.

Complexity of the microenvironment of lung adenocarcinoma (LUAD) poses significant challenges in its clinical management. Systematic bioinformatic analysis of the Ras-association domain family (RASSF) identified RASSF2 as a potential tumour suppressor in LUAD. This study aims to investigate its clinical significance and functional mechanisms in LUAD. CCK-8, EdU, and colony formation assays were performed to investigate the impact of RASSF2 overexpression on the proliferative capacity of LUAD cells. Transwell and wound healing assays were performed to explore the significance of RASSF2 on LUAD cell migration and invasion. RNA sequencing analysis was conducted on three methylation-positive and three methylation-negative LUAD tissue samples to establish the underlying mechanism of RASSF2 methylation in LUAD. Functional studies indicated that RASSF2 overexpression significantly inhibited the proliferation, migration, and invasion of LUAD cells. Patients with RASSF2 promoter hypermethylation exhibited a significantly shorter overall survival than those without. RNA-seq of three pairs of LUAD tissue samples further demonstrated that RASSF2 methylation is associated with upregulation of the NF-κB signalling pathway and dysregulation of T-cell activation pathways. This study confirmed the tumour-suppressive role of RASSF2 in LUAD and suggests its potential as an immunotherapeutic target, thus providing new insights into LUAD treatment strategies.

Penile squamous cell carcinoma (PSCC) can affect men of any age, but we know little about the differences between non-old and old patients with PSCC, which severely limits the precise diagnosis and treatment of PSCC. We collected 2 non-old and 3 old PSCC samples and performed single-cell RNA sequencing and single-cell TCR-Seq analysis. All samples were subjected to UMAP clustering, and subcluster analyses were carried out on tumor cells, T cells, and myeloid cells. Furthermore, cell trajectory analyses were completed for tumor cells and T cells. We performed immunohistochemistry for DCN, KITLG, GPX4, and EPCAM and immunofluorescence for CD24 and MIF, as well as Masson staining and β-galactosidase staining on tissues. Macrophages were cultured for flow cytometry to detect the expression of HLA-DR on the cell surface after MIF treatment. We found that tumor cells in older PSCC demonstrated a more pronounced senescence-associated secretory phenotype (SASP) and gave rise to a subcluster of senescence-associated tumor cells, which exhibited stronger malignant features. Interestingly, we observed similar alterations in old head and neck squamous cell carcinoma (HNSC) samples. In addition, older PSCC samples also had more dysfunctional-like CD24 + T cells and more angiogenic macrophages. Finally, we revealed enhanced MIF signaling between fibroblasts and other cells to be another significant feature of aging PSCC. Our study systematically addressed the effects of aging on PSCC and identified IL1B as a potential prognostic marker for PSCC, offering a framework for the classification management and treatment of PSCC patients.

Angiotensin-converting enzyme 2 (ACE2) has been implicated as an oncogene in certain cancer types; however, there is a lack of analysis on the role of ACE2 in the predictive value for prognosis and immunotherapy response in various tumor types. This study used data from the Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER 2.0), cBioPortal, and ROC Plotter databases to analyze the expression, prognosis, and immune cell infiltration of ACE2 in various tumor types. Furthermore, we analyzed the correlation between the expression of ACE2 and clinicopathological characteristics in 119 pairs of colorectal cancer (CRC) tissues using immunohistochemistry analysis, and then conducted the in vitro experiments to verify the role of ACE2 in the migration and proliferation of CRC cells. We found that ACE2 was highly expressed in CRC tissues compared with adjacent normal tissues, and that CRC patients with high ACE2 expression levels showed poor survival. Additionally, combined bioinformatics and qRT-PCR analysis identified a strong negative correlation between ACE2 expression and natural killer cell infiltration in CRC. Meanwhile, ACE2 expression was significantly elevated in patients resistant to anti-CTLA-4 and anti-PD-L1 therapy and was linked to poor prognosis. In vitro experiments showed that silencing ACE2 inhibits the proliferation and invasion of CRC cells. These results highlight ACE2's involvement in CRC pathogenesis and cancer-immune interactions, positioning it as a promising prognostic and therapeutic biomarker in CRC.

Lactoferrin (LF), an innate immunity molecule, showed a strikingly high expression level in the human prostate compared to other tissues and organs, indicating a significant role in prostate physiology. Despite the tumor-suppressive role of lactoferrin established in other malignancies, we reveal its paradoxical oncogenic function in prostate cancer through an androgen receptor (AR)-LF-ferroptosis axis. Utilizing Lf -/- TRAMP genetic mouse models, proteomics, TCGA-PARD data, and single-cell RNA-seq, we demonstrate that AR directly binds the LF promoter, driving LF expression, which in turn upregulates ferritin (FTH1/FTL) expression and suppresses p53-ALOX12-mediated ferroptosis in prostate cancer. Crucially, Lf deficiency delayed tumor progression and intensified ferroptotic stress in the TRAMP mice, while iron supplementation accelerated carcinogenesis-effects rescued by Lf knockout. Mechanistically, lactoferrin shields prostate cancer cells from iron-induced ferroptosis by maintaining iron-redox homeostasis. Preclinical targeting of this axis suggested a potential therapeutic strategy, as suppressed tumor growth in prostate cancer xenograft was observed following LF knockdown coupled with ferroptosis induction (via IKE) and androgen receptor inhibition (via enzalutamide). This work defines lactoferrin as: (i) an AR-regulated ferroptosis suppressor, (ii) a regulator of prostate cancer's "iron addiction," and (iii) a candidate target for therapeutic exploitation of iron-metabolic vulnerability.

BackgroundImmune escape remains a major challenge in cancer immunotherapy. Transfer RNA (tRNA)-derived small RNA (tsRNA) represents a novel class of non-coding RNAs generated from tRNA cleavage, regulating gene expression at transcriptional and translational levels. These tsRNAs exhibit diverse biological functions, including immune modulation, metabolic disorders, and cell death. Despite their critical involvement in tumor progression, the role of tsRNAs in Natural killer (NK) cells related to immune escape within colorectal cancer (CRC) has not been revealed yet.MethodsHigh-throughput sequencing and the tRFexplorer database were utilized to compare the profiles of CRC and normal tissues. Techniques such as RT-qPCR, western blotting, and flow cytometry were employed to assess gene and protein expression. The Cell Counting Kit-8 assay, colony formation assay, and apoptosis analysis were used to evaluate tumor heterogeneity. Differential gene expression between the tRF-3021a inhibitor and negative control (NC) in HCT116 cells was quantified and characterized using RNA sequencing.ResultsWe identified 3’ tRF-AlaCGC (tRF-3021a) as significantly upregulated in CRC tissues. Major histocompatibility complex class I related chain A (MICA) is an important and stress-induced ligand of the natural killer group 2 member D receptor (NKG2D) that is expressed in various cancer cells. MICA undergoes post-translational modifications that regulate their expression as they are called membrane-bound MICA (mMICA) at the cancer cell surface. mMICA is a ligand that induces the activation of NK cells. Proteolytic cleavage of mMICA by A Disintegrin Metalloproteinase Domains (ADAMs) is the underlying mechanism in CRC. Mechanistically, tRF-3021a promotes proteolytic cleavage of mMICA by upregulating ADAM10, generating soluble MICA (sMICA). Elevated sMICA acts as a decoy ligand for NKG2D receptors on NK cells, impairing cytotoxicity and facilitating immune escape. Functional assays confirmed that tRF-3021a knockdown enhances NK cell-mediated CRC cell killing, while overexpression promotes CRC proliferation and inhibits apoptosis. Clinically, tRF-3021a is elevated in CRC tissues, serum exosomes, and cell lines, cleaved by ANG, demonstrating diagnostic potential. In vivo, experiments provided further evidence that inhibition of tRF-3021a reduce tumorigenicity.ConclusionOur findings reveal tRF-3021a as a novel biomarker and therapeutic target for CRC immunotherapy.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is necessary to maintain stability of EBV episomes, EBV replication, and causes host genomic instability and promotes tumor cells survival. Recent studies have shown that viruses utilize liquid-liquid phase separation (LLPS) within host cells to form sub-cellular compartments known as "virus factories". Prion-like domains (PrLDs), which resemble structural domains of low complexity, are shown to drive LLPS in vivo. In the current study, a PrLD is identified in EBNA1 and aggregation of EBNA1 proteins is observed in EBV-positive tumors. EBNA1 condensate interacting molecules are examined and are found that EBNA1 interacts with the splicing factor SRSF1 to regulate alternative splicing of SRRM1 and promote tumor progression. Deleting the EBNA1 PrLD results in defects in protein aggregation, LLPS, alternative splicing regulation, and nasopharyngeal carcinoma cells proliferation. Targeting the PrLD of EBNA1 inhibits the formation of protein aggregation, promotes alternative splicing of SRRM1, and inhibits the progression of nasopharyngeal carcinoma. Here, we report for the first time that EBNA1, a protein from the human oncogenic virus EBV, is a prion-like protein, combining algorithm prediction and experimental validation. That implies a possible molecular pathogenic mechanism of EBNA1 in neurodegenerative diseases.

Metastasis is a critical feature of malignant tumors and a major cause of treatment failure and poor prognosis. This complex process primarily involves the rearrangement of the cytoskeleton. Among several cytoskeleton‑associated signaling pathways, the ras homolog family (Rho) and Rho‑associated coiled‑coil containing protein kinase (ROCK) signaling pathway serves a key role in cytoskeleton regulation as it controls intracellular actin dynamics and cytoskeletal remodeling to mediate cell movement. Long non‑coding RNAs (lncRNAs), known to serve important roles in tumorigenesis and metastasis, have been shown to regulate the Rho/ROCK pathway. lncRNAs modulate the Rho/ROCK pathway by sponging microRNAs or directly binding to proteins, thereby mediating tumor metastasis. Additionally, lncRNAs can be encapsulated in exosomes and transferred from donor cells to recipient cells, where they regulate components of the Rho/ROCK signaling pathway and further promote the metastatic potential. Based on their functional significance, Rho/ROCK signaling pathway‑associated lncRNAs may serve as novel tumor biomarkers and therapeutic targets. The present review summarizes the role and mechanism of Rho/ROCK signaling pathway‑associated lncRNAs in tumor metastasis, which may offer novel avenues for the diagnosis and treatment of metastatic cancer.

The incidence of breast cancer continues to increase annually, posing a significant challenge for countries worldwide in terms of its prevention and treatment. Therefore, identifying novel therapeutic targets for breast cancer is urgently needed. The peroxiredoxin (PRDX) family is regarded as a good diagnostic marker for various tumors. However, the expression and prognostic significance of PRDX family members in breast cancer remain unclear and require systematic investigation. By using bioinformatic tools such as UALCAN, TIMER2.0, Human Protein Atlas Project (HPA), Gene Set Cancer Analysis (GSCA), and the cBioportal database, we systematically analyzed the expression pattern, prognostic value, methylation status and immune infiltrating association of PRDX gene family members in breast cancer. Through comprehensive analysis, we found that PRDX4 has good prognostic value and is closely related to immune infiltration, and further exploration of its oncogenic function in breast cancer is warranted. Subsequently, we performed a series of cellular assays to explore the potential role of PRDX4 in the progression of breast cancer. We demonstrated that PRDX4 promoted the proliferation, invasion, metastasis, and inhibited the apoptosis of breast cancer cells. In addition, PRDX4 expression was associated with the half maximal inhibitory concentration (IC50) of neratinib which primarily targets human epidermal growth factor receptor 2 (HER2) and showed good binding in molecular docking. Our subsequent experiments showed that the PRDX4-HER2 axis may serve as a potential combined target for neratinib therapy. Our findings suggest that PRDX4 may be a potential diagnostic and prognostic marker for breast cancer, and targeting PRDX4 could represent a novel strategy to improve the efficacy of targeted therapy for patients with HER2-positive breast cancer.

BACKGROUND:U2AF2 (U2 small nuclear ribonucleoprotein auxiliary factor 2), a crucial spliceosome component regulating RNA splicing, plays a dual role in T-cell function and tumorigenesis. This study integrated multi-omics analysis with experimental validation to elucidate the oncogenic mechanisms of U2AF2 in colon adenocarcinoma (COAD). METHODS:U2AF2 expression and its clinical significance were analysed using publicly available COAD transcriptomic and clinical datasets. Single-cell RNA sequencing (scRNA-seq) of COAD tissues and multiplex immunofluorescence were used to assess the association between U2AF2 expression and tumour immune microenvironment composition. The in vitro functional consequences of U2AF2 knockdown on proliferation, migration, and apoptosis were evaluated in COAD cell lines (HCT116, HCT8) using specific assays. RESULTS:The results revealed that splicing factors play a key role in viral infection and regulating of T cell function in the CD4+ cell subsets. U2AF2 mRNA and protein expression were significantly upregulated in COAD patients and were strongly associated with poor prognosis. U2AF2 also exhibited high diagnostic efficiency in COAD and predicted poor overall and disease-free survival. Our study also revealed that high U2AF2 expression was significantly correlated with decreased infiltration levels in CD4+ T cells. Furthermore, U2AF2 knockdown significantly inhibited COAD cell proliferation and migration, while promoting apoptosis. CONCLUSIONS:We demonstrate U2AF2's dual oncogenic mechanisms, driving malignant transformation through aberrant RNA splicing and fostering immunosuppression by reshaping the tumour immune landscape. These findings establish U2AF2 as a promising novel therapeutic target and prognostic biomarker for COAD.

The peroxiredoxin (PRDX) family, also known as the peroxidase family, consists of six members that participate in a variety of essential bio-processes in carcinogenesis. However, their molecular role in lung adenocarcinoma (LUAD) has not been systematically explored. Using bioinformatic tools, we systematically analyzed the expression, prognostic value and drug sensitivity of the PRDX gene family members in LUAD. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression of PRDX1 in both LUAD tissues and cells. Cell Counting Kit-8 (CCK-8) assay was applied to detect the half-maximal inhibitory concentration (IC50) of osimertinib in LUAD. A series of cellular drug assays, including 5-Ethynyl-2'-deoxyuridine (EdU), colony formation, and apoptosis assays, were performed to explore the correlation of PRDX1 with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity by using EGFR-mutant and wild-type LUAD cell lines. Among all the PRDX family members, PRDX1 has a promising prognostic value and is associated with EGFR mutations, as verified by experiments conducted on collected LUAD specimens. In addition, pathway enrichment analysis suggested that PRDX1 expression positively correlated with DNA repair, which is often considered to be inextricably linked to drug resistance in tumor cells. Thus, we validated the correlation between PRDX1 and EGFR-TKI sensitivity through a series of in vitro experiments and found that PRDX1 inhibition along with osimertinib treatment resulted in synergistic inhibition of tumor growth. Moreover, we found that PRDX1 was negatively correlated with the immune infiltration of dendritic cells (DCs) in the tumor microenvironment (TME) of LUAD, further suggesting an oncogenic role of PRDX1. This study demonstrates that high PRDX1 expression could be a potential diagnostic and prognostic marker of LUAD, and the strategy of PRDX1 knockdown provides new insights into improving the therapeutic sensitivity of EGFR-TKI in patients with LUAD.

N7-methylguanosine (m7G) is an important RNA modification involved in epigenetic regulation that is commonly observed in both prokaryotic and eukaryotic organisms. Their influence on the synthesis and processing of messenger RNA, ribosomal RNA, and transfer RNA allows m7G modifications to affect diverse cellular, physiological, and pathological processes. m7G modifications are pivotal in human diseases, particularly cancer progression. On one hand, m7G modification-associated modulate tumour progression and affect malignant biological characteristics, including sustained proliferation signalling, resistance to cell death, activation of invasion and metastasis, reprogramming of energy metabolism, genome instability, and immune evasion. This suggests that they may be novel therapeutic targets for cancer treatment. On the other hand, the aberrant expression of m7G modification-associated molecules is linked to clinicopathological characteristics, including tumour staging, lymph node metastasis, and unfavourable prognoses in patients with cancer, indicating their potential as tumour biomarkers. This review consolidates the discovery, identification, detection methodologies, and functional roles of m7G modification, analysing the mechanisms by which m7G modification-associated molecules contribute to tumour development, and exploring their potential clinical applications in cancer diagnostics and therapy, thereby providing innovative strategies for tumour identification and targeted treatment.

Dendritic cells (DCs) are the most powerful antigen-presenting cells (APCs) within the tumour microenvironment (TME), where they orchestrate T cell-mediated anti-tumour immunity and can also be reprogrammed to promote the progression of tumours in the TME. Extracellular vesicles (EVs) are very small and they are secreted by cells and wrapped in lipid bilayers that shuttle bioactive cargoes, including proteins, nucleic acids, and metabolites, to recipient cells, thereby influencing the progression of diseases, including cancer. DC-derived EVs (DC-EVs) play pivotal roles in the TME by mediating crosstalk with other immune and stromal cells to modulate inflammatory responses, angiogenesis, cell death, and immune evasion, thereby regulating the development and progression of tumours. In recent years, engineered DC-EVs have been widely used for cancer therapies, including cancer immunotherapy, chemotherapy, photodynamic therapy, and gene therapy. This review summarises the comprehensive roles of DC-EVs in tumourigenesis and the application of engineered DC-EVs in cancer therapy, potentially providing readers with a new theoretical basis for tumour-targeted therapy.

Kidney renal clear cell carcinoma (KIRC) is a highly aggressive malignant tumor, and its occurrence and progression are influenced by tumor microenvironment (TME). CD159A, a natural killer (NK) cell inhibitory receptor, has emerged as a critical immune checkpoint in TME. We conducted a comprehensive multi-omics analysis of CD159A expression, prognostic significance, and functional enrichment in KIRC. Additionally, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were employed to perform CD159A expression in the Xiangya KIRC validation cohort. Furthermore, in vitro experiments were evaluated through cell proliferation, colony formation, and flow cytometry (FC) analysis of apoptosis in KIRC cell lines. Our study found that CD159A expression was significantly upregulated in KIRC tissues compared to normal tissues, as confirmed by TCGA data and the Xiangya KIRC validation cohort. In machine learning analyses, the biological significance of the regulatory network risk factors of the CD159A-HLA-E pathway is immunosuppressive receptors or abnormal antigen presentation that may promote immune escape. Elevated CD159A levels were observed in NK cells and CD8+ T cells infiltrating KIRC by single-cell RNA sequencing analysis. A positive correlation between CD159A and NK/CD8+ T cell infiltration was observed, and higher CD159A expression in KIRC patients receiving anti-PD-1/PD-L1 immunotherapy was associated with improved outcomes. In vitro experiments demonstrated that silencing CD159A significantly suppressed proliferation, colony formation and induced apoptosis in KIRC cells. Our research highlights the critical role of CD159A as a key immune checkpoint in KIRC progression and immune evasion, suggesting its potential as a prognostic and immunotherapy biomarker.

Transfer RNA (tRNA)-derived fragments, a new type of tRNA-derived small RNA (tsRNA), can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational levels. tsRNAs are not only degradation fragments but also have biological functions, including those in immune inflammation, metabolic disorders, and cell death. tsRNA dysregulation is closely associated with multiple diseases, including various cancers and acute pancreatitis (AP). AP is a common gastrointestinal disease, and its incidence increases annually. AP development is associated with tsRNAs, which regulate cell injury and induce inflammation, especially pyroptosis and ferroptosis. Notably, serum tRF36 has the potential to serve as a non-invasive diagnostic biomarker and leads to pancreatic acinar cell ferroptosis causing inflammation to promote AP. We show the characteristics of tsRNAs and their diagnostic value and function in AP, and discuss the potential opportunities and challenges of using tsRNAs in clinical applications and research.

Transfer RNA-derived small RNAs (tsRNAs) play crucial regulatory roles in tumour biology; however, their potential as biomarkers for colorectal cancer (CRC) remains underexplored. Plasma samples from 123 patients with CRC and 79 healthy controls (HCs) were collected for this study. Exosomes were extracted from plasma, validated, and tRF-3004a levels were detected using quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between plasma-derived exosomal tRF-3004a expression levels and clinicopathological parameters was analysed using the chi-square test. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of plasma-derived exosomal tRF-3004a. The results showed that compared with HCs, plasma-derived exosomal tRF-3004a was significantly elevated in patients with CRC and decreased after surgery. Moreover, high tRF-3004a expression was significantly associated with lymph node metastasis, tumour node-metastasis staging, carcinoembryonic antigen (CEA) levels, and nerve/vascular invasion in patients with CRC. ROC analysis revealed that plasma-derived exosomal tRF-3004a demonstrated promising diagnostic utility for CRC, with an area under the curve (AUC) of 0.819 (sensitivity, 0.691; specificity, 0.861). The combination of CEA and carbohydrate antigen 19 - 9 (CA19-9) levels increased the AUC to 0.867. The results of this study demonstrate that plasma-derived exosomal tRF-3004a may serve as a novel diagnostic biomarker for CRC.

Head and neck squamous cell carcinoma (HNSCC) ranks as the eighth most prevalent malignancy globally and has the eighth greatest fatality rate when compared to all other forms of cancer. The inhibitor of apoptosis protein (IAP) family comprises a collection of apoptosis-negative modulators characterized by at least one single baculovirus IAP repeat (BIR) domain in its N-terminal region. While the involvement of the IAP family is associated with the initiation and progression of numerous tumours, its specific role in HNSCC remains poorly understood. Thus, this study aimed to comprehensively examine changes in gene expression, immunomodulatory effects, prognosis, and functional enrichment of HNSCC utilising bioinformatics analysis. Elevated levels of distinct IAP family members were observed to varying degrees in HNSCC, with high BIRC2 expression indicating a worse prognosis. Additionally, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to probe the enrichment of gene expression and biological processes related to the IAP family in HNSCC. The infiltration levels of immune cells were shown to be strongly associated with the IAP gene expression, as determined by subsequent analysis. Hence, BIRC2 could be an effective immunotherapy target for HNSCC. Collectively, novel knowledge of the biological roles and prognostic implications of IAP family members in HNSCC is presented in this study.

Colorectal cancer (CRC) is a type of gastrointestinal cancer with high morbidity and mortality rates, and is often accompanied by distant metastases. Metastasis is a major cause of shortened survival time and poor treatment outcomes for patients with CRC. However, the molecular mechanisms underlying the metastasis of CRC remain unclear. Exosomes are a class of small extracellular vesicles that originate from almost all human cells and can transmit biological information (e.g., nucleic acids, lipids, proteins, and metabolites) from secretory cells to target recipient cells. Recent studies have revealed that non-coding RNAs (ncRNAs) can be released by exosomes into the tumour microenvironment or specific tissues, and play a pivotal role in tumorigenesis by regulating a series of key molecules or signalling pathways, particularly those involved in tumour metastasis. Exosomal ncRNAs have potential as novel therapeutic targets for CRC metastasis, and can also be used as liquid biopsy biomarkers because of their specificity and sensitivity. Therefore, further investigations into the biological function and clinical value of exosomal ncRNAs will be of great value for the prevention, early diagnosis, and treatment of CRC metastasis.

Platelets are a significant component of the cell population in the tumour microenvironment (TME). Platelets influence other immune cells and perform cross-talk with tumour cells, playing an important role in tumour development. Extracellular vesicles (EVs) are small membrane vesicles released from the cells into the TME. They can transfer biological information, including proteins, nucleic acids, and metabolites, from secretory cells to target receptor cells. This process affects the progression of various human diseases, particularly cancer. In recent years, several studies have demonstrated that platelet-derived extracellular vesicles (PEVs) can help regulate the malignant biological behaviours of tumours, including malignant proliferation, resistance to cell death, invasion and metastasis, metabolic reprogramming, immunity, and angiogenesis. Consequently, PEVs have been identified as key regulators of tumour progression. Therefore, targeting PEVs is a potential strategy for tumour treatment. Furthermore, the extensive use of nanomaterials in medical research has indicated that engineered PEVs are ideal delivery systems for therapeutic drugs. Recent studies have demonstrated that PEV engineering technologies play a pivotal role in the treatment of tumours by combining photothermal therapy, immunotherapy, and chemotherapy. In addition, aberrant changes in PEVs are closely associated with the clinicopathological features of patients with tumours, which may serve as liquid biopsy markers for early diagnosis, monitoring disease progression, and the prognostic assessment of patients with tumours. A comprehensive investigation into the role and potential mechanisms of PEVs in tumourigenesis may provide novel diagnostic biomarkers and potential therapeutic strategies for treating human tumours.