Oxidative stress and inflammation in breast cancer: Mechanistic interactions and clinical implications

Table 2 Tumor microenvironment components involved in oxidative stress and inflammation in breast cancer

Cell type/component	ROS/redox features	Inflammatory mediators (examples)	Net effect on tumor biology
M1 TAMs	Higher ROS levels, pro-oxidant phenotype	TNF-α, IL-12, reactive nitrogen species	Anti-tumor immunity, tumor cell killing, but also tissue damage in chronic settings
M2 TAMs	Lower ROS due to increased antioxidant enzymes; redox state supports survival	IL-10, TGF-β, CCL2	Immune suppression, promotion of angiogenesis, EMT and metastasis
MDSCs	ROS production combined with arginase and nitric oxide synthase activity	IL-10, TGF-β	T-cell dysfunction, immune evasion, support of metastatic spread
Neutrophils (N1/N2)	Burst ROS production, neutrophil extracellular traps; phenotype shaped by local redox and cytokine milieu	CXCL1, CXCL8/IL-8, TNF-α	Both pro-tumor and anti-tumor roles can promote angiogenesis and metastasis when chronic
Cancer-associated fibroblasts (CAFs)	Altered antioxidant enzymes; EcSOD silencing increases extracellular ROS	TGF-β, growth factors (HGF), matrix-remodeling molecules	ECM remodeling, stiff stroma, immune exclusion, enhanced invasion and drug resistance
Endothelial cells	ROS-mediated endothelial dysfunction under hypoxia and inflammation	VEGF-A, adhesion molecules, chemokines	Pathological angiogenesis, abnormal vasculature, impaired drug delivery
Cancer stem cells	Controlled ROS at low-to-moderate levels, strong Nrf2-driven antioxidant capacity	Variable interaction with TAMs and CAFs via cytokines and exosomes	Maintenance of stemness, resistance to chemo/radiotherapy, relapse and metastasis

TAM: Tumor-associated macrophage; MDSC: Myeloid-derived suppressor cell; EMT: Epithelial-mesenchymal transition; ECM: Extracellular matrix; ROS: Reactive oxygen species; EcSOD: Extracellular superoxide dismutase; HGF: Hepatocyte growth factor; TNF-α: Tumor necrosis factor-α; IL: Interleukin; Nrf2: Nuclear factor erythroid 2-releated factor 2.