Critical Reviews in Oncology/Hematology, Год журнала: 2024, Номер 197, С. 104348 - 104348
Опубликована: Апрель 6, 2024
Язык: Английский
International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 653 - 667
Опубликована: Янв. 1, 2025
In recent years, with an increasingly profound comprehension of the tumor microenvironment, it has been discovered that constituent cells within immune such as macrophages, CD4+T cells, and CD8+T interact in manners conducive to tumorigenesis progression. Exosomes play a pivotal role essential mediators for intercellular material exchange signal transmission this context. Tumor cell-derived exosomes carrying cargo PD-L1 ncRNAs engage induce cytotoxic responses facilitate evasion, thereby promoting advancement. When combined current checkpoint inhibitors like anti-PD-L1/PD-1 therapy, enhancing cell function through exosomal pathways while monitoring augmenting therapeutic effects can significantly improve efficacy. This review delineates crucial derived from both microenvironment along their impact mechanisms on cells. Furthermore, summarizes potential clinical treatment realm when integrated existing immunotherapy methods-particularly exploring feasibility translation alongside engineering materials science techniques.
Язык: Английский
Процитировано
1
Molecular Cancer, Год журнала: 2025, Номер 24(1)
Опубликована: Фев. 14, 2025
Extracellular vesicles (EVs), nanoscale secreted by cells, have attracted considerable attention in recent years due to their role tumor immunomodulation. These facilitate intercellular communication transporting proteins, nucleic acids, and other biologically active substances, they exhibit a dual development immune evasion mechanisms. Specifically, EVs can assist cells evading surveillance attack impairing cell function or modulating immunosuppressive pathways, thereby promoting progression metastasis. Conversely, also transport release immunomodulatory factors that stimulate the activation regulation of system, enhancing body's capacity combat malignant diseases. This functionality presents promising avenues targets for immunotherapy. By examining biological characteristics influence on immunity, novel therapeutic strategies be developed improve efficacy relevance cancer treatment. review delineates complex immunomodulation explores potential implications approaches, aiming establish theoretical foundation provide practical insights advancement future EVs-based immunotherapy strategies.
Язык: Английский
Процитировано
1
Cancer Medicine, Год журнала: 2023, Номер 12(15), С. 16405 - 16415
Опубликована: Июль 27, 2023
Metastatic castration-resistant prostate cancer (mCRPC) remains fatal and incurable, despite a variety of treatments that can delay disease progression prolong life. Immune checkpoint therapy is promising treatment. However, emerging evidence suggests exosomal programmed necrosis ligand 1 (PD-L1) directly binds to PD-1 on the surface T cells in drain lineage lymph nodes or neutralizes administered PD-L1 antibodies, resulting poor response anti-PD-L1 mCRPC.Western blotting immunofluorescence were performed compare levels exosomes derived from different cells. PC3 subcutaneously injected into nude mice, then ELISA assay was used detect human specific purified mouse serum. The function CD8+ detected by cell mediated tumor killing FACS analysis. A subcutaneous xenograft model established using RM1, with without every 3 days, size weight analyzed evaluate effect PD-L1.Herein, we found exosomal-PD-L1 taken up expressing low PD-L1, thereby protecting them T-cell killing. Higher highly malignant DU145 lines. Moreover, PD-L1-low-expressing LNCaP line inhibited CD8-T growth rate RM1-derived tumors decreased after knockdown cells, whereas recovered following tail vein injection. Furthermore, serum mice PCa tumors, mainly present exosomes.In summary, share synergistically against through exosomes. Inhibition exosome secretion prevention sorting may improve therapeutic therapy.
Язык: Английский
Процитировано
18
ACS Nano, Год журнала: 2024, Номер unknown
Опубликована: Сен. 25, 2024
The tumor microenvironment (TME) plays a crucial role in cancer progression and immune evasion, partially mediated by the activity of TME-derived exosomes. These extracellular vesicles are pivotal shaping responses through transfer proteins, lipids, nucleic acids between cells, facilitating complex interplay that promotes growth metastasis. This review delves into dual roles exosomes TME, highlighting both their immunosuppressive functions emerging therapeutic potential. Exosomes can inhibit T cell function promote escape carrying immune-modulatory molecules, such as PD-L1, yet they also hold promise for therapy vehicles delivering antigens costimulatory signals. Additionally, discusses intricate crosstalk among various types within influencing to immunotherapies. Moreover, this highlights current challenges future directions. Collectively, elucidating detailed mechanisms which mediate offers promising avenue revolutionizing treatment. Understanding these interactions allows development targeted therapies manipulate exosomal pathways enhance system's response tumors.
Язык: Английский
Процитировано
5
Small, Год журнала: 2024, Номер unknown
Опубликована: Апрель 19, 2024
Prostate cancer (PCa) has become a public health concern in elderly men due to an ever-increasing number of estimated cases. Unfortunately, the available treatments are unsatisfactory because lack durable response, especially advanced disease states. Extracellular vesicles (EVs) lipid-bilayer encircled nanoscale that carry numerous biomolecules (e.g., nucleic acids, proteins, and lipids), mediating transfer information. The past decade witnessed wide range EV applications both diagnostics therapeutics. First, EV-based non-invasive liquid biopsies provide biomarkers various clinical scenarios guide treatment; EVs can facilitate grading staging patients for appropriate treatment selection. Second, play pivotal role pathophysiological processes via intercellular communication. Targeting key molecules involved EV-mediated tumor progression proliferation, angiogenesis, metastasis, immune escape, drug resistance) is potential approach curbing PCa. Third, promising carriers. Naïve from sources engineered delivery systems have paved way development new modalities. This review discusses recent advancements application therapies highlights functional materials as novel interventions
Язык: Английский
Процитировано
4
Cancers, Год журнала: 2024, Номер 16(16), С. 2797 - 2797
Опубликована: Авг. 8, 2024
This review delves into the intricate roles of interleukin-8 (IL-8) and its receptors, CXCR1 CXCR2, in prostate cancer (PCa), particularly castration-resistant (CRPC) metastatic CRPC (mCRPC). emphasizes crucial role tumour microenvironment (TME) inflammatory cytokines promoting progression response to cell targeting agents. IL-8, acting through C-X-C chemokine receptor type 1 (CXCR1) 2 (CXCR2), modulates multiple signalling pathways, enhancing angiogenesis, proliferation, migration cells. highlights shift PCa research focus from solely cells non-cancer-cell components, including vascular endothelial cells, extracellular matrix, immune dynamic interactions within TME. The immunosuppressive nature TME significantly influences resistance emerging therapies. Current treatment modalities, androgen deprivation therapy chemotherapeutics, encounter persistent are complicated by cancer’s notably “immune-cold” nature, which limits system tumour. These challenges underscore critical need for novel approaches that both overcome enhance engagement therapeutic potential inhibiting IL-8 is explored, with studies showing enhanced sensitivity treatments, radiation inhibitors. Clinical trials, such as ACE trial, demonstrate efficacy combining CXCR2 inhibitors existing offering significant benefits, especially patients resistant PCa. also addresses chemokines, noting complexity precision avoid side effects optimize outcomes.
Язык: Английский
Процитировано
4
Cancers, Год журнала: 2025, Номер 17(1), С. 141 - 141
Опубликована: Янв. 4, 2025
Background/Objectives: Prostate cancer (PCa) is characterised by its progression to a metastatic and castration-resistant phase. tumour cells release small extracellular vesicles or exosomes which are taken up target can potentially facilitate growth metastasis. The present work studies the effect of from cell lines that representative different stages disease on tumoral phenotype PC3 cells. Methods: Exosomes were isolated ultracentrifugation human prostate epithelial (RWPE-1) androgen-dependent PCa (LNCaP) (CRPC) with moderate (DU145) high (PC3) capacity. biophysical biochemical properties as well their effects viability migration. Results: study shows heterogeneity in size, presenting some them two types populations; both populations, larger size those derived smaller non-tumourigenic detected. Differences found physical healthy cells, between most aggressive disease. highest gamma-glutamyl transferase (GGT) activity was observed differences pro-metalloproteinases (MMP) detected capacity respect treatment own increased Conclusion: represent promising field research diagnosis, prognosis, cancer.
Язык: Английский
Процитировано
0
Extracellular Vesicle, Год журнала: 2025, Номер 5, С. 100063 - 100063
Опубликована: Янв. 18, 2025
Язык: Английский
Процитировано
0
Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)
Опубликована: Март 21, 2025
Abstract Small extracellular vesicles (sEVs) play a critical role in the progression, diagnosis, and treatment of prostate cancer (PCa), particularly within tumor microenvironment (TME). Acting as novel biomarkers agents for targeted biological therapy, sEVs contribute significantly to improving patient survival. These transport variety biomolecules, including proteins, nucleic acids, lipids, which are instrumental remodeling TME, facilitating intercellular communication, influencing key processes such growth, metastasis, therapy resistance. A thorough understanding sEV heterogeneity, their biogenesis, characteristics, potential applications, is essential. Recent advances have illuminated origins, formation processes, molecular cargo PCa-derived (PCa-sEVs), enhancing our disease progression. Furthermore, show promise diagnostic markers, with applications early detection prognostic assessment PCa. Therapeutically, natural engineered offer versatile drug delivery, gene immunomodulation, underscoring PCa management. This review delves into substantial clinical practices Graphical
Язык: Английский
Процитировано
0
International Journal of Genomics, Год журнала: 2025, Номер 2025(1)
Опубликована: Янв. 1, 2025
Prostate cancer (PCa) continues to pose substantial clinical challenges, with molecular heterogeneity significantly impacting therapeutic decision‐making and disease trajectories. Emerging evidence implicates protein lactylation—a novel epigenetic regulatory mechanism—in oncogenic processes, though its prognostic relevance in PCa remains underexplored. Through integrative bioinformatics interrogation of lactylation‐associated signatures, we established correlations using multivariable feature selection methodologies. Initial screening via differential expression analysis (limma package) coupled Cox proportional hazards modeling revealed 11 survival‐favorable regulators 16 hazard‐associated elements linked biochemical recurrence. To enhance predictive precision, ensemble machine learning frameworks were implemented, culminating a 10‐gene lactylation signature demonstrating robust discriminative capacity (concordance index = 0.738) across both primary (TCGA‐PRAD) external validation cohorts (DKFZ). Multivariable regression confirmed the score’s independence, exhibiting prominent associations clinicopathological parameters including tumor staging metastatic potential. The developed clinical‐molecular nomogram achieved superior accuracy (C − > 0.7) through synergistic integration biological covariates. Tumor microenvironment deconvolution uncovered distinct immunological landscapes, high‐risk stratification correlating enriched stromal infiltration immunosuppressive phenotypes. Pathway enrichment analyses implicated chromatin remodeling processes cytokine‐mediated inflammatory cascades as potential mechanistic drivers divergence. Therapeutic vulnerability profiling demonstrated response patterns: low‐risk patients exhibited enhanced immune checkpoint inhibitor responsiveness, whereas subgroups showed selective chemosensitivity docetaxel mitoxantrone. Functional PC‐3 models AK5 silencing induced proapoptotic effects, suppressed migration invasion, modulated regulation CD276 coexpression. These multimodal findings position dynamics, particularly AK5‐mediated pathways, promising targets biomarkers management.
Язык: Английский
Процитировано
0