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:Tuning cellular metabolism for cancer virotherapy.
Tuning cellular metabolism for cancer virotherapy.
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溶瘤病毒(OVs)因其直接裂解肿瘤和诱导抗肿瘤免疫的能力,代表了一种新兴的免疫治疗策略。然而,短暂持续性和中等疗效等障碍需要创新方法。代谢重塑最近作为一项战略性干预措施受到关注,其中OVs或联合方案可以重编程肿瘤和免疫细胞代谢,以增强病毒复制和溶瘤作用。在这篇综述中,我们总结了通过战略性重编程肿瘤和免疫细胞代谢来增强基于OV的免疫治疗的最新进展。具体策略包括工程化病毒以靶向癌细胞的糖酵解、谷氨酰胺分解和核苷酸合成途径,从而促进病毒复制和肿瘤细胞死亡。此外,重编程T细胞和NK细胞的脂质、氨基酸和碳水化合物代谢显示出增强抗肿瘤效应的前景。进一步讨论了相关见解,为代谢增强型溶瘤平台的临床实施铺平道路,包括平衡代谢调节以限制抗病毒反应,同时促进病毒持续性和肿瘤清除。
Oncolytic viruses (OVs) represent an emerging immunotherapeutic strategy owing to their capacity for direct tumor lysis and induction of antitumor immunity.
However, hurdles like transient persistence and moderate efficacy necessitate innovative approaches. Metabolic remodeling has recently gained prominence as a strategic intervention, wherein OVs or combination regimens could reprogram tumor and immune cell metabolism to enhance viral replication and oncolysis.
In this review, we summarize recent advances in strategic reprogramming of tumor and immune cell metabolism to enhance OV-based immunotherapies. Specific tactics include engineering viruses to target glycolytic, glutaminolytic, and nucleotide synthesis pathways in cancer cells, boosting viral replication and tumor cell death.
Additionally, rewiring T cell and NK cell metabolism of lipids, amino acids, and carbohydrates shows promise to enhance antitumor effects.
Further insights are discussed to pave the way for the clinical implementation of metabolically enhanced oncolytic platforms, including balancing metabolic modulation to limit antiviral responses while promoting viral persistence and tumor clearance.
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