Unlocking the secrets of the immunopeptidome: MHC molecules, ncRNA peptides, and vesicles in immune response

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 29, 2025

The immunopeptidome, a diverse set of peptides presented by Major Histocompatibility Complex (MHC) molecules, is critical component immune recognition and response. This review article delves into the mechanisms peptide presentation MHC particularly emphasizing roles ncRNA-derived extracellular vesicles (EVs) in shaping immunopeptidome landscape. We explore established emerging insights molecule interactions with peptides, including dynamics loading, transport, influence cellular genetic variations. highlights novel research on non-coding RNA (ncRNA)-derived which challenge conventional views antigen processing role EVs transporting these thereby modulating responses at remote body sites. not only challenges but also opens up new avenues for understanding responses. Furthermore, we discuss implications developing therapeutic strategies, cancer immunotherapy. By conducting comprehensive analysis current literature advanced methodologies immunopeptidomics, this aims to deepen complex interplay between system, offering perspectives potential diagnostic applications. Additionally, provide mechanism enhanced surface highlight pathway their systemic distribution, potentially altering surveillance landscapes.

Language: Английский

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Enhanced efficacy of dual chimeric antigen receptor-T cells targeting programmed death-ligand 1 and cancer-associated fibroblasts in colorectal cancer in vitro

CytoJournal, Journal Year: 2025, Volume and Issue: 22, P. 29 - 29

Published: March 6, 2025

Colorectal cancer (CRC) presents significant treatment challenges, including immune evasion and tumor microenvironment (TME) suppression. Chimeric antigen receptor (CAR) T-cell therapy has shown promise in hematologic malignancies, but its effectiveness against solid tumors is hampered by the detrimental effects of TME. This article aims to explore potential bispecific CAR T cells targeting programmed death-ligand 1 (PD-L1) cancer-associated fibroblasts (CAFs) CRC treatment. Dual-targeted CAR-T PD-L1 CAF were engineered using GV400 lentiviral vector. Programmed death-1 (PD-1)/nanobody (Nb) fibroblast activation protein (FAP)/Nb-encoding vectors generated, produced through a three-plasmid system 293T cells. Human peripheral blood mononuclear (PBMCs) separated, transduced with these vectors, then expanded. Functional characterization was performed enzyme-linked immunosorbent assay (ELISA), Western blot analysis, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, cell counting kit-8 (CCK-8) assay. Migration invasion assays conducted Transwell chambers assess ability FAP-PD-1/Nb migrate toward invade extracellular matrix. We developed dual-targeted incorporating Nbs, which continuously secreted PD-1/Nb. confirmed PD-1/Nb expression cells, no untreated (UTD) group (P < 0.01). Flow cytometry showed significantly higher cluster differentiation (CD)25 CD69 upon stimulation FAP-positive target compared other groups TUNEL, CCK-8 revealed that exhibited superior cytotoxicity proliferation inhibition HCT116 ELISA demonstrated increased interferon-gamma necrosis factor-alpha levels reduced interleukin-10 0.01), suggesting enhanced cytokine modulation antitumor immunity. Compared single-target UTD, notably Matrigel penetration Safety tests minimal normal PBMCs, indicating favorable safety. study successfully their activity immunomodulatory on novel therapeutic strategy established technology for CRC.

Language: Английский

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Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 15, 2024

Exosomes are nanoscale vesicles of cellular origin. One the main characteristics exosomes is their ability to carry a wide range biomolecules from parental cells, which important mediators intercellular communication and play an role in physiological pathological processes. have advantages biocompatibility, low immunogenicity, biodistribution. As researchers' understanding has increased, various strategies been proposed for use diagnosing treating diseases. Here, we provide overview biogenesis composition exosomes, describe relationship between disease progression, focus on as biomarkers early screening, monitoring, guiding therapy refractory diseases such tumors neurodegenerative We also summarize current applications especially engineered efficient drug delivery, targeted therapies, gene immune vaccines. Finally, challenges potential research directions clinical application discussed. In conclusion, emerging molecule that can be used diagnosis treatment diseases, combined with multidisciplinary innovative solutions, will applications.

Language: Английский

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Role of Extracellular Vesicles in Crohn’s Patients on Adalimumab Who Received COVID-19 Vaccination

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8853 - 8853

Published: Aug. 14, 2024

Crohn’s disease (CD) is a type of inflammatory bowel (IBD) affecting the gastrointestinal tract that can also cause extra-intestinal complications. Following exposure to mRNA vaccine BNT162b2 (Pfizer-BioNTech) encoding SARS-CoV-2 Spike (S) protein, some patients experienced lack response biological drug Adalimumab and recrudescence disease. In CD in progression, resistant considered therapy, an abnormal increase intestinal permeability was observed, more often with modulated expression different proteins such as Aquaporin 8 (AQP8) tight junctions (e.g., ZO-1, Claudin1, Claudin2, Occludin), especially during flares. The aim this study investigate how could interfere IBD therapy contribute exacerbation. We investigated role transported by extracellular vesicles (EVs), impact various EVs components, namely, exosomes (EXOs) microvesicles (MVs), modulating molecules involved exacerbation CD, which remains unknown.

Language: Английский

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Wildfire-Relevant Woodsmoke and Extracellular Vesicles (EVs): Alterations in EV Proteomic Signatures Involved in Extracellular Matrix Degradation and Tissue Injury in Airway Organotypic Models

Environmental Research, Journal Year: 2024, Volume and Issue: unknown, P. 120395 - 120395

Published: Nov. 1, 2024

Language: Английский

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