Neutrophils, the most abundant white blood cells, play a dual role in cancer progression. While they can promote tumor growth, metastasis, and immune suppression, they also exhibit anti-tumorigenic properties by attacking cancer cells and enhancing immune responses. This review explores the complex interplay between neutrophils and the tumor microenvironment (TME), highlighting their ability to switch between pro- and anti-tumor phenotypes based on external stimuli. Pro-tumorigenic neutrophils facilitate tumor growth through mechanisms such as neutrophil extracellular traps (NETs), secretion of pro-inflammatory cytokines, and immune evasion strategies. They contribute to angiogenesis, tumor invasion, and metastasis by releasing vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Conversely, anti-tumor neutrophils enhance cytotoxicity by generating reactive oxygen species (ROS), promoting antibody-dependent cell-mediated cytotoxicity (ADCC), and activating other immune cells such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Recent advances in neutrophil-based drug delivery systems have harnessed their tumor-homing capabilities to improve targeted therapy. Neutrophil-mimicking nanoparticles and membrane-coated drug carriers offer enhanced drug accumulation in tumors, reduced systemic toxicity, and improved therapeutic outcomes. Additionally, strategies to modulate neutrophil activity, such as inhibiting their immunosuppressive functions or reprogramming them towards an anti-tumor phenotype, are emerging as promising approaches in cancer immunotherapy. Understanding neutrophil plasticity and their interactions with the TME provides new avenues for therapeutic interventions. Targeting neutrophil-mediated mechanisms could enhance existing cancer treatments and lead to the development of novel immunotherapies, ultimately improving patient survival and clinical outcomes.
中性粒细胞作为数量最丰富的白细胞，在癌症进展中扮演着双重角色。它们既能促进肿瘤生长、转移和免疫抑制，也能通过攻击癌细胞和增强免疫应答发挥抗肿瘤作用。本综述探讨中性粒细胞与肿瘤微环境（TME）之间复杂的相互作用，重点阐述其在外界刺激下可在促肿瘤与抗肿瘤表型间转换的特性。促肿瘤中性粒细胞通过中性粒细胞胞外陷阱（NETs）、促炎细胞因子分泌及免疫逃逸等机制促进肿瘤生长，并通过释放血管内皮生长因子（VEGF）和基质金属蛋白酶（MMPs）参与血管生成、肿瘤侵袭和转移过程。反之，抗肿瘤中性粒细胞通过产生活性氧（ROS）、促进抗体依赖性细胞介导的细胞毒性（ADCC），以及激活细胞毒性T淋巴细胞（CTLs）和自然杀伤（NK）细胞等免疫细胞来增强细胞毒性。基于中性粒细胞的药物递送系统研究取得新进展，利用其肿瘤归巢特性可提升靶向治疗效果。中性粒细胞仿生纳米颗粒和膜包被药物载体能增强药物在肿瘤部位的富集，降低全身毒性并改善疗效。此外，通过抑制免疫抑制功能或将其重编程为抗肿瘤表型等调控中性粒细胞活性的策略，正成为癌症免疫治疗的新兴方向。理解中性粒细胞的可塑性及其与肿瘤微环境的相互作用，为治疗干预开辟了新途径。靶向中性粒细胞介导的机制有望增强现有癌症治疗效果，推动新型免疫疗法的开发，最终提升患者生存率和临床预后。
Neutrophils and Neutrophil-Based Drug Delivery Systems in Anti-Cancer Therapy
肿瘤(癌症)患者之家