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:Synergistic Anti-Tumor Efficacy of Modified FOLFIRINOX and NK Cell Therapy in Pancreatic Ductal Adenocarcinoma.
Synergistic Anti-Tumor Efficacy of Modified FOLFIRINOX and NK Cell Therapy in Pancreatic Ductal Adenocarcinoma.
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mFOLFIRINOX 联合 NK 细胞疗法对胰腺导管腺癌(PDAC)显示出增强的抗肿瘤活性,可能改善临床结局。
胰腺导管腺癌(PDAC)进展迅速、易早期转移且对常规治疗耐药,是肿瘤学领域的严峻挑战。开发有效且毒性更低的治疗方法对于改善PDAC预后至关重要。本研究旨在探究改良FOLFIRINOX(mFOLFIRINOX)联合自然杀伤(NK)细胞疗法在PDAC模型中的协同抗肿瘤潜力。
通过体外和体内实验,评估mFOLFIRINOX治疗后NK细胞活化配体和诱导凋亡受体表达变化。随后将NK细胞用于mFOLFIRINOX预处理的PDAC细胞,评估NK细胞细胞毒性、免疫应答和肿瘤进展,采用体外实验和小鼠体内模型。
mFOLFIRINOX治疗可显著上调PDAC细胞系及体内采集肿瘤细胞的NK细胞活化配体和诱导凋亡受体,从而提高其对NK细胞介导细胞毒作用的敏感性。与任一单药治疗相比,mFOLFIRINOX联合NK细胞疗法可增强所有细胞系的细胞裂解。体内研究显示,联合疗法显著抑制肿瘤生长并延长小鼠模型生存期。
mFOLFIRINOX联合NK细胞疗法可增强对PDAC的抗肿瘤活性,可能改善临床结局。这些发现强调仍需进一步研究以优化该联合策略,推动临床应用。
We evaluated changes in NK-cell-activating ligands and apoptosis-inducing receptor expression after mFOLFIRINOX treatment both in vitro and in vivo. Subsequently, NK cells were administered to mFOLFIRINOX-pre-treated PDAC cells to assess NK cell cytotoxicity, immune responses, and tumor progression both in vitro and in vivo mouse models.
Treatment with mFOLFIRINOX led to the significant upregulation of NK-cell-activating ligands and apoptosis-inducing receptors across the PDAC cell lines and tumor cells collected in vivo, thereby enhancing their susceptibility to NK-cell-mediated cytotoxicity. In comparison with either treatment alone, mFOLFIRINOX and NK cell combination therapy resulted in enhanced cytolysis in all cell lines. In vivo studies demonstrated that combination therapy substantially inhibited tumor growth and prolonged survival in a mouse model.
mFOLFIRINOX combined with NK cell therapy demonstrates enhanced antitumor activity against PDAC, potentially improving clinical outcomes. These findings highlight the need for continued research to optimize this combination strategy for clinical utility.
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