biostudies-literatureShamekh MMEgyptian Cultural and Educational BureauKarolinska InstitutetIngaBritt och Arne Lundbergs Forskningsstiftelse (Ingabritt and Arne Lundberg Research Foundation)IngaBritt och Arne Lundbergs Forskningsstiftelse114https://www.ebi.ac.uk/biostudies/studies/S-EPMC12847883biostudies-literatureUnknown17(1)Glucocorticoids (GCs) are known for their anti-inflammatory potential, which includes the macrophage polarization into an anti-inflammatory and tissue remodeling state. GCs are routinely co-administered to cancer patients to alleviate the side effects of chemotherapy. However, it is not well known if GCs can modulate tumor-associated macrophages (TAMs) to promote tumor progression. Here, we show that dexamethasone (DEX) induces dose-dependent differentiation of THP-1 monocyte-derived anti-tumorigenic (M1) macrophages into pro-tumorigenic (M2-like) macrophages, even in the presence of M1 cues, and that DEX can repolarize fully differentiated M1 macrophages into an M2-like state. These macrophages have a cytokine profile similar to the pro-tumorigenic (M2) macrophages and can stimulate the pCell death & diseaseDexamethasone drives macrophage repolarization linked to increased triple-negative breast cancer aggressiveness.PMC12847883LU2022-0025Nalvarte IShamekh MMLindqvist BfalseDexamethasone drives macrophage repolarization linked to increased triple-negative breast cancer aggressiveness.Glucocorticoids (GCs) are known for their anti-inflammatory potential, which includes the macrophage polarization into an anti-inflammatory and tissue remodeling state. GCs are routinely co-administered to cancer patients to alleviate the side effects of chemotherapy. However, it is not well known if GCs can modulate tumor-associated macrophages (TAMs) to promote tumor progression. Here, we show that dexamethasone (DEX) induces dose-dependent differentiation of THP-1 monocyte-derived anti-tumorigenic (M1) macrophages into pro-tumorigenic (M2-like) macrophages, even in the presence of M1 cues, and that DEX can repolarize fully differentiated M1 macrophages into an M2-like state. These macrophages have a cytokine profile similar to the pro-tumorigenic (M2) macrophages and can stimulate the p2025-01-01T00:00:00Z2025 Dec2026-06-09T06:56:36.121Z2026-06-09T03:11:50.996ZS-EPMC128478834141309310.1038/s41419-025-08363-9