Exosomes derived from rapamycin‐treated 4T1 breast cancer cells induced polarization of macrophages to M1 phenotype

Abstract

M2 macrophages are the most prevalent type in the tumor microenvironment and their polarization to M1 type can be used as a potential cancer immunotherapy. Here, we investigated the role of tumor microenvironment and particularly purified exosomes in M2 to M1 macrophage polarization. Rapamycin treatment on triple‐negative breast cancer cells (TNBC) was performed. Tumor cells‐derived exosomes (called texosomes) were isolated and characterized using scanning electron microscopy, transmission electron microscopy, dynamic light scattering, high‐performance liquid chromatography, Fourier transform infrared, and Western blot assays. M2 mouse peritoneal macrophages were treated with rapamycin or rapamycin‐texosome. Then, M1/M2 phenotype‐specific marker genes and proteins were measured to assess the degree of M2 to M1 polarization. Finally, nitric oxide (NO) production, phagocytosis, and efferocytosis assays were assessed to verify the functionality of the polarized macrophages. Purified rapamycin‐texosomes significantly increased the expression of the M1 markers (Irf5, Nos2, and CD86) and decreased M2 markers (Arg, Ym1, and CD206). In addition, the levels of M1‐specific cytokines tumor necrosis factor alpha and interleukin 1β (IL‐1β) were increased, whereas the levels of M2 specific cytokines IL‐10 and transforming growth factor beta were declined. Furthermore, texosome treatment increased NO concentration and phagocytosis and decreased efferocytosis indicating M1 polarization. These findings suggest rapamycin‐texosomes can induce M2 to M1 macrophages polarization as a potential immunotherapy for TNBC.

Unveiling Novel Avenues in mTOR-Targeted Therapeutics: Advancements in Glioblastoma Treatment

“…This treatment also led to increased levels of M1-specific cytokines (TNF-alpha, IL-1β), decreased levels of M2-specific cytokines (IL-10, TGF-beta), elevated nitric oxide (NO) concentration, enhanced phagocytosis, and reduced efferocytosis, ultimately promoting M1 polarization. These findings suggest the potential of this approach as an immunotherapy for triple-negative breast cancer cells [106]. Additionally, Rapamycin-encapsulated U937 macrophage-derived exosomes mimic nanoparticles-in-microspheres (RNM) that were formulated with poly-lactic-co-glycolic acid (PLGA) and utilized in the treatment of hemangioma.…”

Tumor-derived extracellular vesicles regulate macrophage polarization: role and therapeutic perspectives

“…This enhanced macrophage phagocytosis. These findings lift the immunosuppression of the tumor by promoting macrophage M1 polarization, which offers a fresh approach to clinical tumor therapy ( 97 ).…”