Related Experiment Video
Updated: Jan 24, 2026
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
MiR-146a-armed exosomes reverse immunosuppressive networks in NSCLC by dual-targeting of MYD88/STAT3 and PD-L1 axes
Mina Alimohammadi1, Safa Tahmasebi1, Davar Amani1
1Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background:
MiR-146a has been found to be a tumor suppressor and is downregulated in NSCLC cells. This study investigated the effects of delivering miR-146a via tumor-derived exosomes (TEX-MiR-146a) on the behavior of malignant cells and immunological modulation in NSCLC models.
Methods:
miR-146a expression was evaluated in A-549 and normal MRC-5 lung epithelial cells. Exosomes were isolated from A-549 cells, loaded with a miR-146a mimic, and characterized for size, morphology, surface markers, and loading efficiency. In vitro, the functional effects of TEXmiR-146a were compared to controls using tests for cell survival, apoptosis, migration, invasion, wound healing, colony formation, and gene expression. Co-culture immunological assays, including T cell subset and cytokine profiling, were also performed using patient-derived peripheral blood mononuclear cells (PBMCs).
Results:
TEXmiR-146a efficiently loaded miR-146a into cells (60.1 % ± 4.0 efficiency, P < 0.0001). Treatment with TEXmiR-146a (25 μg/ml) significantly reduced the viability of A-549 cells by ∼51 % after 48 h (P < 0.0001). Cell migration and invasion were inhibited by >50 %, with migrating cells reduced to 116.7 ± 7.09 (P < 0.001) and invading cells to 171.7 ± 6.028 (P < 0.001), respectively, compared to controls. Pro-apoptotic genes Bax/Bcl-2 (P = 0.0002) and Caspase-3 were upregulated (P = 0.0003), while metastatic and immunoregulatory genes VEGF-A, MMP-9, STAT3, MYD88, and PD-L1 were downregulated (all P < 0.05). In patient PBMCs, TEXmiR-146a increased the frequency of cytotoxic CD8+ T cells (24.75 ± 1.23 % versus 20.15 ± 1.26 %, P < 0.0001) and decreased Treg cells (2.01 ± 1.22 % versus 4.04 ± 1.72 %, P = 0.015) compared to the TEX group, alongside a significant reduction in TGF-β (P = 0.01).
Conclusion:
Exosomal delivery of miR-146a effectively restores tumor suppressor functions and reverses immunosuppressive networks in NSCLC by dual-targeting key oncogenic and immunomodulatory axes, presenting a potent cell-free immunotherapeutic strategy.
Insights
Tumor-derived exosomes loaded with miR-146a (TEX-MiR-146a) suppress non-small cell lung cancer (NSCLC) progression. This novel immunotherapy approach also modulates the immune microenvironment, enhancing anti-tumor responses.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- MicroRNA-146a (miR-146a) acts as a tumor suppressor, but its expression is reduced in non-small cell lung cancer (NSCLC).
- This study explores the therapeutic potential of delivering miR-146a using tumor-derived exosomes (TEX-MiR-146a) in NSCLC models.
Purpose of the Study:
- To investigate the efficacy of exosomal miR-146a delivery in inhibiting NSCLC cell behavior.
- To evaluate the immunomodulatory effects of TEX-MiR-146a on the tumor microenvironment.
Main Methods:
- miR-146a mimic loaded into A-549 cell-derived exosomes (TEXmiR-146a).
- In vitro assays assessed cancer cell viability, apoptosis, migration, invasion, and gene expression.
- Co-culture assays with patient PBMCs evaluated T cell subsets and cytokine profiles.
Main Results:
- TEXmiR-146a significantly reduced NSCLC cell viability, migration, and invasion.
- Treatment upregulated pro-apoptotic genes and downregulated key metastatic and immunoregulatory genes (VEGF-A, MMP-9, STAT3, MYD88, PD-L1).
- TEXmiR-146a increased cytotoxic CD8+ T cells and decreased regulatory T cells and TGF-β in patient PBMCs.
Conclusions:
- Exosomal delivery of miR-146a effectively restores tumor suppressor functions in NSCLC.
- This strategy reverses immunosuppressive networks by targeting oncogenic and immunomodulatory pathways.
- TEX-MiR-146a represents a promising cell-free immunotherapeutic approach for NSCLC.
More Related Videos
10:18Author Spotlight: Magnetic Fluorescent Bead-Based Dual-Reporter Flow Analysis of PDL1-Vaxx Peptide Vaccine-Induced Antibody Blockade of the PD-1/PD-L1 Interaction
Published on: July 7, 2023
08:49Exosomal miRNA Analysis in Non-small Cell Lung Cancer NSCLC Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool
Published on: May 27, 2016
Related Concept Videos
02:26Protein Networks
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:18Moments of Inertia for an Area about Inclined Axes
01:31Muscles that Move the Arm
The pectoralis major has two origins. Its clavicular head originates on the medial half of the clavicle. In contrast, the sternocostal head originates on the costal cartilages of ribs 1-6, the sternum, and the aponeurosis of the external oblique of the...
01:09Angular Momentum and Principle Axes of Inertia
To put this equation into simpler terms, it can be reconfigured using rectangular coordinates. This involves choosing an alternative set of XYZ axes that are arbitrarily inclined with respect to the reference frame. The process of deriving the rectangular...
01:26PD Controller: Design
Designing a continuous-data controller requires selecting and linking components like adders and integrators, which are fundamental in Proportional,...
01:25Relative Motion Analysis using Rotating Axes
However, to express the relative position of point B relative to point A, an additional frame of reference, denoted as x'y', is necessary. This additional frame not only translates but also rotates relative to the fixed frame, making it...