Dutta Abhishek, Bhagat Shrikrishna, Paul Swastika, Katz Jonathan P, Sengupta Debomita, Bhargava Dharmendra
Exsure, Kalinga Institute of Industrial Technology, KIIT Rd, Patia, Bhubaneswar 751024, Odisha, India.
Department of Gastroenterology, 928 BRB II/III, 421 Curie Blvd, University of Pennsylvania, Philadelphia, PA 19104, USA.
Vaccines (Basel). 2023 May 26;11(6):1028. doi: 10.3390/vaccines11061028.
Neutrophils are the most abundant immune cells and make up about 70% of white blood cells in human blood and play a critical role as the first line of defense in the innate immune response. They also help regulate the inflammatory environment to promote tissue repair. However, in cancer, neutrophils can be manipulated by tumors to either promote or hinder tumor growth depending on the cytokine pool. Studies have shown that tumor-bearing mice have increased levels of neutrophils in peripheral circulation and that neutrophil-derived exosomes can deliver various cargos, including lncRNA and miRNA, which contribute to tumor growth and degradation of extracellular matrix. Exosomes derived from immune cells generally possess anti-tumor activities and induce tumor-cell apoptosis by delivering cytotoxic proteins, ROS generation, HO or activation of Fas-mediated apoptosis in target cells. Engineered exosome-like nanovesicles have been developed to deliver chemotherapeutic drugs precisely to tumor cells. However, tumor-derived exosomes can aggravate cancer-associated thrombosis through the formation of neutrophil extracellular traps. Despite the advancements in neutrophil-related research, a detailed understanding of tumor-neutrophil crosstalk is still lacking and remains a major barrier in developing neutrophil-based or targeted therapy. This review will focus on the communication pathways between tumors and neutrophils, and the role of neutrophil-derived exosomes (NDEs) in tumor growth. Additionally, potential strategies to manipulate NDEs for therapeutic purposes will be discussed.
中性粒细胞是最丰富的免疫细胞,占人类血液中白细胞的约70%,在先天性免疫反应中作为第一道防线发挥关键作用。它们还有助于调节炎症环境以促进组织修复。然而,在癌症中,中性粒细胞可被肿瘤操纵,根据细胞因子库的情况促进或阻碍肿瘤生长。研究表明,荷瘤小鼠外周循环中的中性粒细胞水平升高,且中性粒细胞衍生的外泌体可递送包括长链非编码RNA和微小RNA在内的各种货物,这些货物有助于肿瘤生长和细胞外基质降解。免疫细胞衍生的外泌体通常具有抗肿瘤活性,并通过递送细胞毒性蛋白、产生活性氧、激活靶细胞中的Fas介导的凋亡或激活Fas介导的凋亡来诱导肿瘤细胞凋亡。工程化的类外泌体纳米囊泡已被开发用于将化疗药物精确递送至肿瘤细胞。然而,肿瘤衍生的外泌体可通过形成中性粒细胞胞外陷阱加重癌症相关血栓形成。尽管中性粒细胞相关研究取得了进展,但对肿瘤-中性粒细胞相互作用的详细了解仍然缺乏,并且仍然是开发基于中性粒细胞的疗法或靶向疗法的主要障碍。本综述将重点关注肿瘤与中性粒细胞之间的通讯途径,以及中性粒细胞衍生的外泌体(NDEs)在肿瘤生长中的作用。此外,还将讨论为治疗目的操纵NDEs的潜在策略。
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