Obeagu Emmanuel Ifeanyi
Department of Biomedical and Laboratory Science, Africa University, Mutare, Zimbabwe.
Ann Med Surg (Lond). 2025 May 12;87(6):3682-3690. doi: 10.1097/MS9.0000000000003361. eCollection 2025 Jun.
Neutrophils, essential components of the innate immune system, exhibit remarkable plasticity in the tumor microenvironment, shifting between anti-tumoral (N1) and pro-tumoral (N2) phenotypes. This functional dichotomy is particularly significant in breast cancer, where N1 neutrophils contribute to tumor suppression by enhancing cytotoxicity and immune activation, while N2 neutrophils promote tumor progression through immunosuppression, angiogenesis, and metastasis. The tumor microenvironment, driven by factors such as TGF-β, IL-6, and hypoxia, orchestrates this polarization, profoundly influencing disease progression and therapeutic outcomes. The interplay between neutrophil polarization and breast cancer immunotherapy presents both challenges and opportunities. Pro-tumoral N2 neutrophils often hinder the efficacy of immune checkpoint inhibitors and other immunotherapies by suppressing T-cell function and facilitating tumor immune evasion. Conversely, strategies to reprogram neutrophils toward the N1 phenotype, including TGF-β inhibitors, CXCR2 antagonists, and epigenetic modulators, show promise in restoring anti-tumoral activity. Novel approaches, such as nanoparticle-mediated delivery of neutrophil-targeting agents, further expand the potential for precision immunotherapy by selectively modulating neutrophil phenotypes.
中性粒细胞是先天性免疫系统的重要组成部分，在肿瘤微环境中表现出显著的可塑性，在抗肿瘤（N1）和促肿瘤（N2）表型之间转换。这种功能二分法在乳腺癌中尤为重要，其中N1中性粒细胞通过增强细胞毒性和免疫激活来促进肿瘤抑制，而N2中性粒细胞则通过免疫抑制、血管生成和转移来促进肿瘤进展。由转化生长因子-β、白细胞介素-6和缺氧等因素驱动的肿瘤微环境协调这种极化，深刻影响疾病进展和治疗结果。中性粒细胞极化与乳腺癌免疫治疗之间的相互作用既带来了挑战，也带来了机遇。促肿瘤的N2中性粒细胞通常通过抑制T细胞功能和促进肿瘤免疫逃逸来阻碍免疫检查点抑制剂和其他免疫疗法的疗效。相反，将中性粒细胞重编程为N1表型的策略，包括转化生长因子-β抑制剂、CXCR2拮抗剂和表观遗传调节剂，在恢复抗肿瘤活性方面显示出前景。新型方法，如纳米颗粒介导的中性粒细胞靶向剂递送，通过选择性调节中性粒细胞表型进一步扩大了精准免疫治疗的潜力。
