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:VG161 activates systemic antitumor immunity in pancreatic cancer models as a novel oncolytic herpesvirus expressing multiple immunomodulatory transgenes.
VG161 activates systemic antitumor immunity in pancreatic cancer models as a novel oncolytic herpesvirus expressing multiple immunomodulatory transgenes.
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VG161是首个携带多种协同抗肿瘤免疫调节因子的重组溶瘤单纯疱疹病毒1型。在此,我们报告其抗肿瘤机制,从而为即将在胰腺癌中开展的临床应用提供坚实的理论基础。总体而言,VG161介导的抗肿瘤结果通过多种技术协作进行分析,即单细胞测序、气流辅助解吸电喷雾电离质谱成像(AFADSI-MSI)和Nanostring技术。在体外,VG161与免疫检查点抑制剂(ICIs)联合的疗效已成功显示可通过改变肿瘤免疫和重塑肿瘤微环境(TME)代谢来赋予长期抗肿瘤效应。在治疗前后检测的患者样本中,细胞功能通路和细胞亚型发生了显著变化,包括上调的CD8+ T细胞和NK 细胞。更重要的是,自VG161注射给药以来,已出现显著的抗肿瘤信号。总之,VG161可在胰腺癌模型中系统性激活获得性免疫和先天性免疫,并改善肿瘤免疫微环境,这表明VG161与其他疗法联合在胰腺癌治疗中具有进一步探索的价值。
The VG161 represents the first recombinant oncolytic herpes simplex virus type 1 carrying multiple synergistic antitumor immuno-modulating factors.
Here, we report its antitumor mechanisms and thus provide firm theoretical foundation for the upcoming clinical application in pancreatic cancer. Generally, the VG161-mediated antitumor outcomes were analyzed by a collaboration of techniques, namely the single-cell sequencing, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADSI-MSI) and nanostring techniques.
In vitro, the efficacy of VG161 together with immune checkpoint inhibitors (ICIs) has been successfully shown to grant a long-term antitumor effect by altering tumor immunity and remodeling tumor microenvironment (TME) metabolisms. Cellular functional pathways and cell subtypes detected from patient samples before and after the treatment had undergone distinctive changes including upregulated CD8+ T and natural killer cells. More importantly, significant antitumor signals have emerged since the administration of VG161 injection.
In conclusion, VG161 can systematically activate acquired and innate immunity in pancreatic models, as well as improve the tumor immune microenvironment, indicative of strong antitumor potential. The more robusting antitumor outcome for VG161 monotherapy or in combination with other therapies on pancreatic cancer is worth of being explored in further clinical trials.
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