Neutrophils and cancer immunotherapy: Potential mechanisms and challenges in breast cancer – a narrative review

Neutrophils, the most abundant white blood cells in circulation, are gaining recognition for their intricate roles in cancer biology, particularly in breast cancer. These cells can exhibit dual behavior, either promoting tumor progression through immunosuppressive mechanisms or combating cancer by enhancing anti-tumor immune responses. Tumor-associated neutrophils (TANs) are highly plastic, with their phenotype and function influenced by the tumor microenvironment. This duality underscores the complexity of targeting neutrophils for therapeutic purposes in breast cancer immunotherapy. Key mechanisms such as neutrophil extracellular traps (NETs) and immune modulation by TANs are central to their role in breast cancer. NETs contribute to cancer metastasis by facilitating tumor cell adhesion and immune evasion, while TANs can suppress cytotoxic T-cell activity through the release of immunosuppressive mediators like arginase-1 and reactive oxygen species (ROS). Empirical studies have demonstrated that high neutrophil-to-lymphocyte ratios and excessive NET formation are correlated with poor prognosis in breast cancer patients, particularly those with aggressive subtypes such as triple-negative breast cancer.