@article{Alimohammadi:2026:10.1016/j.intimp.2026.116173,
author = {Alimohammadi, M and Tahmasebi, S and Amani, D and Salimi, B and Hajivalili, M and Adcock, IM and Mortaz, E},
doi = {10.1016/j.intimp.2026.116173},
journal = {Int Immunopharmacol},
title = {MiR-146a-armed exosomes reverse immunosuppressive networks in NSCLC by dual-targeting of MYD88/STAT3 and PD-L1 axes.},
url = {http://dx.doi.org/10.1016/j.intimp.2026.116173},
volume = {172},
year = {2026}
}

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TY  - JOUR
AB  - 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 th
AU  - Alimohammadi,M
AU  - Tahmasebi,S
AU  - Amani,D
AU  - Salimi,B
AU  - Hajivalili,M
AU  - Adcock,IM
AU  - Mortaz,E
DO  - 10.1016/j.intimp.2026.116173
PY  - 2026///
TI  - MiR-146a-armed exosomes reverse immunosuppressive networks in NSCLC by dual-targeting of MYD88/STAT3 and PD-L1 axes.
T2  - Int Immunopharmacol
UR  - http://dx.doi.org/10.1016/j.intimp.2026.116173
UR  - https://www.ncbi.nlm.nih.gov/pubmed/41570746
VL  - 172
ER  - 

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