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:Unmasking the potential: mechanisms of neuroinflammatory modulation by oncolytic viruses in glioblastoma.
Unmasking the potential: mechanisms of neuroinflammatory modulation by oncolytic viruses in glioblastoma.
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胶质母细胞瘤是一种侵袭性强且致命的脑肿瘤,在临床上带来巨大挑战,包括分子异质性、高复发率、对常规治疗的耐药性以及跨血脑屏障的治疗渗透有限。胶质母细胞瘤微环境以细胞和非细胞成分之间的动态相互作用为特征,是肿瘤生长和治疗耐药的关键驱动因素。神经炎症性细胞因子,尤其是白细胞介素和肿瘤坏死因子-α,在该微环境中发挥关键作用,促进肿瘤进展和免疫逃逸。本综述聚焦于溶瘤病毒疗法作为一种有前景的治疗途径,重点关注其调节神经炎症反应、诱导局部免疫反应以及将免疫调节因子直接递送至肿瘤部位的潜力。尽管已观察到令人鼓舞的结果,但克服血脑屏障、管理宿主抗病毒免疫以及减轻对正常神经元细胞的潜在风险等挑战仍是临床转化的关键障碍。通过分析溶瘤病毒与胶质母细胞瘤微环境的复杂相互作用,并综合临床前和临床试验的研究结果,本综述为开发基于单独溶瘤病毒疗法或将其与常规疗法、免疫疗法、NK 细胞疗法、CAR-T 细胞疗法和树突状细胞疗法联合使用的个性化且有效的治疗策略提供了可操作的见解。
Glioblastoma, an aggressive and lethal brain tumor, presents enormous clinical challenges, including molecular heterogeneity, high recurrence rates, resistance to conventional therapies, and limited therapeutic penetration across the blood-brain barrier. The glioblastoma microenvironment, characterized by a dynamic interplay of cellular and non-cellular components, is a key driver of tumor growth and therapeutic resistance. Neuroinflammatory cytokines, particularly interleukins and tumor necrosis factor-alpha, play pivotal roles in this microenvironment, contributing to tumor progression and immune evasion. This review highlights oncolytic virotherapy as a promising therapeutic avenue, focusing on its potential to modulate neuroinflammatory responses, induce localized immune reactions, and deliver immunomodulatory factors directly to the tumor site.
While encouraging outcomes have been observed, challenges such as overcoming the blood-brain barrier, managing host antiviral immunity, and mitigating potential risks to normal neuronal cells remain critical barriers to clinical translation.
By analyzing the intricate interactions of oncolytic viruses with the glioblastoma microenvironment and synthesizing findings from preclinical and clinical trials, this review provides actionable insights into developing personalized and effective therapeutic strategies for this aggressive tumor based on oncolytic virotherapy alone or when using it combined with conventional therapies, immunotherapy, natural killer-cell therapy, chimeric antigen receptor-T cell therapy, and dendritic cell therapy.
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