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
非病毒载体介导的叶酸修饰 CKb11 通过调控巨噬细胞极化和 DC 成熟激发抗肿瘤免疫应答
英文原题：Non-viral vector mediated CKb11 with folic acid modification regulates macrophage polarization and DC maturation to elicit immune response against cancer.
查看英文原题
Non-viral vector mediated CKb11 with folic acid modification regulates macrophage polarization and DC maturation to elicit immune response against cancer.
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中文摘要
癌症的免疫抑制性肿瘤微环境（TME）强烈阻碍抗肿瘤免疫应答，从而导致免疫治疗应答令人失望。趋化因子对白细胞的趋化和促进特性，通过增加免疫细胞在TME中的浸润，已引起人们提高免疫治疗效率的兴趣。在本研究中，开发了一种基于DOTAP、MPEG-PCL-MPEG和FA-PEG-PCL-PEG-FA自组装的叶酸（FA）修饰基因递送系统，即F-PPPD，用于递送编码免疫刺激性趋化因子CKb11的质粒。F-PPPD纳米颗粒递送质粒CKb11（pCKb11）导致肿瘤细胞高分泌CKb11，成功激活T细胞，抑制巨噬细胞的M2极化，促进树突状细胞（DCs）成熟，促进自然杀伤（NK）细胞浸润，并抑制肿瘤组织中免疫抑制细胞的浸润。给予F-PPPD/pCKb11也显著抑制了癌症进展。我们的研究展示了一种纳米技术赋能的pCKb11递送，其重塑了免疫抑制性TME，用于癌症治疗。
展开英文摘要原文
The immunosuppressive tumor microenvironment (TME) of cancer strongly hinders the anti-tumor immune responses, thereby resulting in disappointing responses to immunotherapy. Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME. In this study, a folic acid (FA) -modified gene delivery system based on the self-assembly of DOTAP, MPEG-PCL-MPEG, and FA-PEG-PCL-PEG-FA, namely F-PPPD, was developed to deliver plasmids encoding the immunostimulating chemokine CKb11.
The delivery of plasmid CKb11 (pCKb11) by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells, which successfully activated T cells, suppressed the M2 polarization of macrophages, promoted the maturation of dendritic cells (DCs), facilitated the infiltration of natural killer (NK) cells and inhibited the infiltration of immunosuppressive cells in tumor tissues. Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression.
Our study demonstrated a nanotechnology-enabled delivery of pCKb11, that remodeled the immunosuppressive TME, for cancer treatment.
论文信息
- 作者
- Nie W、Yu T、Liu X、Wang B、Li T、Wu Y、Zhou X、Ma L
- 单位
- Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, PR China.China
- 期刊
- Bioactive materials2021 Nov
- 原文标识
- PubMed 33898872 · DOI 10.1016/j.bioactmat.2021.03.031
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