Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Radiation Oncology, Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
Int Immunopharmacol. 2024 Oct 25;140:112788. doi: 10.1016/j.intimp.2024.112788. Epub 2024 Jul 30.
The tumor microenvironment (TME) is intricately associated with cancer progression, characterized by dynamic interactions among various cellular and molecular components that significantly impact the carcinogenic process. Notably, neutrophils play a crucial dual role in regulating this complex environment. These cells oscillate between promoting and inhibiting tumor activity, responding to a multitude of cytokines, chemokines, and tumor-derived factors. This response modulates immune reactions and affects the proliferation, metastasis, and angiogenesis of cancer cells. A significant aspect of their influence is their interaction with the endoplasmic reticulum (ER) stress responses in cancer cells, markedly altering tumor immunodynamics by modulating the phenotypic plasticity and functionality of neutrophils. Furthermore, neutrophil extracellular traps (NETs) exert a pivotal influence in the progression of malignancies by enhancing inflammation, metastasis, immune suppression, and thrombosis, thereby exacerbating the disease. In the realm of immunotherapy, checkpoint inhibitors targeting PD-L1/PD-1 and CTLA-4 among others have underscored the significant role of neutrophils in enhancing therapeutic responses. Recent research has highlighted the potential of using neutrophils for targeted drug delivery through nanoparticle systems, which precisely control drug release and significantly enhance antitumor efficacy. This review thoroughly examines the diverse functions of neutrophils in cancer treatment, emphasizing their potential in regulating immune therapy responses and as drug delivery carriers, offering innovative perspectives and profound implications for the development of targeted diagnostic and therapeutic strategies in oncology.
肿瘤微环境（TME）与癌症进展密切相关，其特征是各种细胞和分子成分之间的动态相互作用，这些相互作用极大地影响了致癌过程。值得注意的是，中性粒细胞在调节这种复杂环境中起着至关重要的双重作用。这些细胞在促进和抑制肿瘤活动之间波动，对多种细胞因子、趋化因子和肿瘤衍生因子作出反应。这种反应调节免疫反应，并影响癌细胞的增殖、转移和血管生成。它们影响的一个重要方面是它们与癌细胞内质网（ER）应激反应的相互作用，通过调节中性粒细胞的表型可塑性和功能，显著改变肿瘤免疫动力学。此外，中性粒细胞胞外诱捕网（NETs）通过增强炎症、转移、免疫抑制和血栓形成来促进恶性肿瘤的进展，从而使疾病恶化。在免疫治疗领域，针对 PD-L1/PD-1 和 CTLA-4 等的检查点抑制剂强调了中性粒细胞在增强治疗反应中的重要作用。最近的研究强调了通过纳米颗粒系统将中性粒细胞用于靶向药物输送的潜力，该系统可精确控制药物释放并显著提高抗肿瘤疗效。这篇综述全面检查了中性粒细胞在癌症治疗中的多种功能，强调了它们在调节免疫治疗反应和作为药物输送载体方面的潜力，为肿瘤学中靶向诊断和治疗策略的发展提供了创新视角和深远影响。
