Obeagu Emmanuel Ifeanyi
Department of Biomedical and Laboratory Science, Africa University, Mutare, Zimbabwe.
Ann Med Surg (Lond). 2025 Jul 18;87(9):5762-5769. doi: 10.1097/MS9.0000000000003609. eCollection 2025 Sep.
Breast cancer (BC) remains a leading cause of cancer-related deaths globally, with the tumor microenvironment (TME) playing a pivotal role in disease progression. Neutrophils, the most abundant white blood cells, have gained attention for their dualistic role in cancer immunity. Two major neutrophil subtypes, N1 and N2, have been identified, each exhibiting distinct functions in the TME. N1 neutrophils are typically associated with anti-tumor immunity, promoting tumor cell clearance through mechanisms such as reactive oxygen species production, cytokine release, and the activation of cytotoxic immune cells. In contrast, N2 neutrophils promote tumor progression, metastasis, and immune suppression by secreting pro-angiogenic factors and recruiting regulatory immune cells like Tregs and myeloid-derived suppressor cells. The polarization of neutrophils into N1 or N2 subtypes is regulated by the dynamic interactions within the TME, including cytokines, hypoxic conditions, and signals from tumor cells. In BC, factors such as IL-8, transforming growth factor-beta, and granulocyte-macrophage colony-stimulating factor drive N2 polarization, contributing to tumor evasion of immune surveillance. Conversely, pro-inflammatory signals can induce N1 polarization, which is often linked to favorable clinical outcomes. However, in aggressive breast cancer subtypes such as triple-negative breast cancer, the TME is more conducive to N2 polarization, resulting in poor prognosis and resistance to treatment.
乳腺癌（BC）仍然是全球癌症相关死亡的主要原因，肿瘤微环境（TME）在疾病进展中起着关键作用。中性粒细胞是最丰富的白细胞，因其在癌症免疫中的双重作用而受到关注。已鉴定出两种主要的中性粒细胞亚型，N1和N2，它们在TME中各自表现出不同的功能。N1中性粒细胞通常与抗肿瘤免疫相关，通过产生活性氧、释放细胞因子以及激活细胞毒性免疫细胞等机制促进肿瘤细胞清除。相比之下，N2中性粒细胞通过分泌促血管生成因子和募集调节性免疫细胞如调节性T细胞（Tregs）和髓源性抑制细胞来促进肿瘤进展、转移和免疫抑制。中性粒细胞向N1或N2亚型的极化受TME内的动态相互作用调节，包括细胞因子、缺氧条件和肿瘤细胞发出的信号。在乳腺癌中，白细胞介素-8（IL-8）、转化生长因子-β和粒细胞-巨噬细胞集落刺激因子等因素驱动N2极化，导致肿瘤逃避免疫监视。相反，促炎信号可诱导N1极化，这通常与良好的临床结果相关。然而，在三阴性乳腺癌等侵袭性乳腺癌亚型中，TME更有利于N2极化，导致预后不良和治疗抵抗。
