文章：

通过质粒基因疗法修饰肿瘤微环境以增强免疫

Modification of the tumor microenvironment enhances immunity with plasmid gene therapy 

原文发布日期：2024-02-09 

英文摘要：

Local intratumor delivery with electroporation of low levels of plasmids encoding molecules, induces an antitumor effect without causing systemic toxicity. However, previous studies have predominately focused on the function of the delivered molecule encoded within the plasmid, and ignored the plasmid vector. In this study, we found vectors pUMVC3 and pVax1 induced upregulation of MHC class I (MHC-I) and PD-L1 on tumor cell surface. These molecules participate in a considerable number of immunoregulatory functions through their interactions with and activating inhibitory immune cell receptors. MHC molecules are well-known for their role in antigen (cross-) presentation, thereby functioning as key players in the communication between immune cells and tumor cells. Increased PD-L1 expression on tumor cells is an important monitor of tumor growth and the effectiveness of immune inhibitor therapy. Results from flow cytometry confirmed increased expression of MHC-I and PDL-1 on B16F10, 4T1, and KPC tumor cell lines. Preliminary animal data from tumor-bearing models, B16F10 melanoma, 4T1 breast cancer and KPC pancreatic cancer mouse models showed that tumor growth was attenuated after pUMVC3 intratumoral electroporation. Our data also documented that pSTAT1 signaling pathway might not be associated with plasmid vectors’ function of upregulating MHC-I, PD-L1 on tumor cells. 

摘要翻译： 

通过电穿孔局部瘤内递送低剂量编码分子的质粒可诱导抗肿瘤效应，且不引起全身毒性。然而既往研究主要关注质粒所编码递送分子的功能，忽视了质粒载体本身的作用。本研究发现pUMVC3和pVax1载体能诱导肿瘤细胞表面MHC I类分子（MHC-I）和PD-L1表达上调。这些分子通过与抑制性免疫细胞受体相互作用并激活该受体，参与大量免疫调节功能。MHC分子因其在抗原（交叉）呈递中的作用而广为人知，是免疫细胞与肿瘤细胞间通讯的关键参与者。肿瘤细胞PD-L1表达增加是监测肿瘤生长和免疫抑制剂疗效的重要指标。流式细胞术结果证实B16F10、4T1及KPC肿瘤细胞系中MHC-I与PD-L1表达增加。基于B16F10黑色素瘤、4T1乳腺癌和KPC胰腺癌小鼠荷瘤模型的初步动物数据显示，pUMVC3瘤内电穿孔处理后肿瘤生长受到抑制。我们的数据还表明pSTAT1信号通路可能不参与质粒载体上调肿瘤细胞MHC-I和PD-L1的功能。

原文链接：

Modification of the tumor microenvironment enhances immunity with plasmid gene therapy