Exosomes From Toll-Like Receptor 4-Stimulated Lung Cancer Cells Modulate Macrophage Polarization.

Abstract

Exosomes derived from lung cancer cells play a critical role in modulating the tumour microenvironment, particularly through their effects on macrophage polarization. We investigated how exosomes from A549 lung adenocarcinoma cells, both unstimulated and stimulated with a toll-like receptor 4 (TLR4) agonist, influence the phenotype and function of THP-1 derived macrophages. We used differential centrifugation and immunobead assay to isolate exosomes. Exosomes from unstimulated A549 cells promoted a mixed M1/M2 macrophage phenotype with a bias towards M2 polarization, while exosomes from TLR4-stimulated A549 cells reduced M2 marker expression without affecting M1 polarization. Both types of exosomes increased macrophage phagocytic capacity compared to PMA-differentiated controls, but TLR4-agonists did not increase it further. These findings provide new insights into how TLR agonist-stimulated lung cancer-derived exosomes shape macrophage phenotypes and functions, with implications for understanding tumour-immune interactions and developing novel therapeutic strategies targeting the tumour microenvironment.