Lu Tong, Li Wei
Division of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA 17033, USA.
Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA 17033, USA.
Cancers (Basel). 2025 Jan 24;17(3):384. doi: 10.3390/cancers17030384.
Neutrophils, the most abundant circulating white blood cells, are essential for the initial immune response to infection and injury. Emerging research reveals a dualistic function of neutrophils in cancer, where they can promote or inhibit tumor progression. This dichotomy is influenced by the tumor microenvironment, with neutrophils capable of remodeling the extracellular matrix, promoting angiogenesis, or alternatively inducing cancer cell death and enhancing immune responses. An intriguing yet poorly understood aspect of neutrophil-cancer interactions is the phenomenon of neutrophil engulfment by cancer cells, which has been observed across various cancers. This process, potentially mediated by LC3-associated phagocytosis (LAP), raises questions about whether it serves as a mechanism for immune evasion or contributes to tumor cell death through pathways like ferroptosis. This review examines current knowledge on neutrophil development, their roles in cancer, and the mechanisms of LAP in neutrophil engulfment by tumor cells. We discuss how manipulating LAP impacts cancer progression and may represent a therapeutic strategy. We also explore neutrophils' potential as delivery vehicles for cancer therapeutic agents. Understanding the complex functions of tumor-associated neutrophils (TANs) and the molecular mechanisms underlying LAP in cancer may open new avenues for effective therapeutic interventions and mitigate potential risks.
中性粒细胞是循环系统中数量最多的白细胞，对于感染和损伤的初始免疫反应至关重要。新兴研究揭示了中性粒细胞在癌症中的二元功能，它们既可以促进也可以抑制肿瘤进展。这种二分法受肿瘤微环境影响，中性粒细胞能够重塑细胞外基质、促进血管生成，或者诱导癌细胞死亡并增强免疫反应。中性粒细胞与癌症相互作用中一个有趣但尚未得到充分理解的方面是癌细胞吞噬中性粒细胞的现象，这在各种癌症中都有观察到。这个过程可能由LC3相关吞噬作用（LAP）介导，引发了关于它是作为免疫逃逸机制，还是通过铁死亡等途径导致肿瘤细胞死亡的问题。这篇综述探讨了关于中性粒细胞发育、它们在癌症中的作用以及LAP在肿瘤细胞吞噬中性粒细胞中的机制的现有知识。我们讨论了操纵LAP如何影响癌症进展以及可能代表一种治疗策略。我们还探讨了中性粒细胞作为癌症治疗药物递送载体的潜力。了解肿瘤相关中性粒细胞（TANs）的复杂功能以及癌症中LAP的潜在分子机制可能为有效的治疗干预开辟新途径，并降低潜在风险。
