文章：

改良FOLFIRINOX方案与NK细胞疗法在胰腺导管腺癌中的协同抗肿瘤效应

Synergistic Anti-Tumor Efficacy of Modified FOLFIRINOX and NK Cell Therapy in Pancreatic Ductal Adenocarcinoma

原文发布日期：26 August 2025

DOI: 10.3390/cancers17172785

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) presents a formidable challenge in oncology due to its aggressive progression, propensity for early metastasis, and resistance to conventional therapies. The development of effective and less toxic treatments is crucial for improving the prognosis of PDAC. We aimed to investigate the synergistic antitumor potential of modified FOLFIRINOX (mFOLFIRINOX) combined with natural killer (NK) cell therapy in PDAC models. Methods: 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. Results: 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. Conclusions: 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.

摘要翻译： 

背景/目的：胰腺导管腺癌（PDAC）因其进展迅速、早期转移倾向及对常规治疗的耐药性，成为肿瘤学领域的一大难题。开发有效且毒性较低的治疗方法对于改善PDAC预后至关重要。本研究旨在探讨改良FOLFIRINOX方案（mFOLFIRINOX）联合自然杀伤细胞疗法在PDAC模型中的协同抗肿瘤潜力。方法：我们在体外和体内评估了mFOLFIRINOX治疗后NK细胞活化配体及凋亡诱导受体表达的变化。随后，将NK细胞施用于经mFOLFIRINOX预处理的PDAC细胞，通过体外及小鼠体内模型评估NK细胞毒性、免疫应答及肿瘤进展。结果：mFOLFIRINOX治疗显著上调了PDAC细胞系及体内收集的肿瘤细胞中NK细胞活化配体和凋亡诱导受体的表达，从而增强了其对NK细胞介导的细胞毒作用的敏感性。与单一治疗相比，mFOLFIRINOX联合NK细胞疗法在所有细胞系中均表现出更强的细胞溶解作用。体内研究表明，联合疗法在小鼠模型中显著抑制了肿瘤生长并延长了生存期。结论：mFOLFIRINOX联合NK细胞疗法对PDAC展现出增强的抗肿瘤活性，有望改善临床预后。这些发现强调了持续优化该联合策略以推动临床应用的迫切需求。

原文链接：

Synergistic Anti-Tumor Efficacy of Modified FOLFIRINOX and NK Cell Therapy in Pancreatic Ductal Adenocarcinoma