RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Neutrophils in oncolytic virus immunotherapy.
Neutrophils in oncolytic virus immunotherapy.
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溶瘤病毒因其能够在肿瘤内特异性复制、携带治疗基因并通过多种机制调节免疫抑制性肿瘤微环境,已成为一种极具前景的癌症治疗模式。
此外,它们还显示出与免疫检查点抑制剂协同作用的潜力。一项研究报告表明,2000年至2020年间,在临床试验中49.5%的溶瘤病毒采用瘤内给药,35%采用静脉给药。
然而,这两种给药方式都面临重大挑战,尤其是静脉给药,其面临非特异性组织摄取、中和抗体反应以及多种免疫细胞介导的抗病毒效应等问题。尽管针对CD8+ T细胞和NK细胞在溶瘤病毒治疗中抗病毒作用的研究已较为广泛,但中性粒细胞——约占人体外周血白细胞的50%至70%——受到的关注相对较少。中性粒细胞是外周循环中最丰富的白细胞亚群,以其吞噬活性而闻名。除了在细菌和真菌感染中的传统作用外,新兴文献表明中性粒细胞在机体抗病毒反应中也发挥关键作用。鉴于对中性粒细胞在溶瘤病毒治疗中作用的认识存在空白,本文综述了该领域的现有文献,旨在为开发基于溶瘤病毒的癌症疗法以及在未来临床治疗中增强其抗肿瘤疗效提供理论基础。
Oncolytic viruses have emerged as a highly promising modality for cancer treatment due to their ability to replicate specifically within tumors, carry therapeutic genes, and modulate the immunosuppressive tumor microenvironment through various mechanisms.
Additionally, they show potential synergy with immune checkpoint inhibitors. A study report indicates that from 2000 to 2020, 49. 5% of oncolytic viruses were administered intratumorally and 35% intravenously during clinical trials.
However, both administration methods face significant challenges, particularly with intravenous delivery, which encounters issues such as non-specific tissue uptake, neutralizing antibody responses, and antiviral effects mediated by various immune cells. Despite extensive research into the antiviral roles of CD8+ T cells and NK cells in oncolytic virus therapy, neutrophils-constituting approximately 50% to 70% of human peripheral blood leukocytes-have received relatively little attention.
Neutrophils are the most abundant leukocyte subset in peripheral circulation, known for their phagocytic activity. Beyond their traditional roles in bacterial and fungal infections, emerging literature suggests that neutrophils also play a critical role in the body's antiviral responses.
Given the gaps in understanding the role of neutrophils in oncolytic virus therapy, this article reviews current literature on this topic. It aims to provide a theoretical foundation for developing oncolytic virus-based cancer therapies and enhancing their anti-tumor efficacy in future clinical treatments.
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