中国肿瘤生物治疗杂志2026，Vol.33Issue(5)：486-493,8.DOI:10.3872/j.issn.1007-385x.2026.05.002
ALDH1A1 mRNA负载树突状细胞疫苗体外诱导抗鼻咽癌干细胞免疫反应
The specific immune response of dendritic cell vaccine pulsed with ALDH1A1 mRNA on nasopharyngeal carcinoma stem cells in vitro
摘要
Abstract
Objective:To investigate the ability of dendritic cell(DC)vaccine loaded with aldehyde dehydrogenase 1A1(ALDH1A1)mRNA to enhance anti-nasopharyngeal carcinoma stem cell immune responses in vitro.Methods:ALDH1A1 mRNA was transcribed in vitro and electroporated into human peripheral blood-derived DCs to construct ALDH1A1-DC vaccine;EGFP mRNA was used as a transfection control.Flow cytometry was employed to analyze DC phenotypes,lymphocyte subsets,cytotoxic T lymphocyte(CTL)proliferation,and cytokine secretion.ALDH+and ALDH-C666-1 cells were sorted;expression of stem cell markers(CD24,CD133)and stemness-associated genes(OCT4,SOX2,Nanog)was analyzed.The specific cytotoxic capacity induced by ALDH1A1-DC was evaluated using the Cell Counting Kit-8(CCK-8)assay.Results:EGFP-DC exhibited significantly higher fluorescence expression than untransfected DCs(P<0.000 1).Moreover,ALDH1A1-DC significantly enhanced the expression of antigen-presenting molecules HLA-ABC,co-stimulatory molecules CD86,CD40,and CCR7 compared to untransfected DCs(P=0.001 3,P=0.005 9,P=0.000 4,P=0.001 9).Compared with the T lymphocyte group(T)and the DC-T group(DC-induced T lymphocytes),ALDH1A1-DC-induced T lymphocytes(ALDH1A1-DC-T)exhibited the highest proportion of CTL(P<0.000 1),the highest proliferation index(P=0.000 2 and P=0.000 3,respectively),the highest proportions of CD8+CD69+cells(P=0.000 5 and P<0.000 1,respectively),and the highest proportions of CD8+IFN-γ+subsets(P=0.012 6 and P=0.001 9,respectively).CCK-8 assay demonstrated that ALDH1A1-DC-T exhibited significantly enhanced cytotoxicity against ALDH+C666-1 suspension spheres compared to ALDH-spheres(P=0.001 0).Furthermore,ALDH1A1-DC-T elicited the most potent anti-ALDH+C666-1 immune response among all lymphocyte groups tested(P=0.001 0 and P<0.000 1,respectively).However,HLA-ABC blockade significantly attenuated this specific cytotoxicity(P<0.000 1).Conclusion:mRNA transfected into DCs can be translated into protein and promote the maturation of DCs and enhance the ability of DCs to induce specific CTL immune response.关键词
肿瘤干细胞/乙醛脱氢酶1A1/树突状细胞/细胞毒性T淋巴细胞/鼻咽癌Key words
cancer stem cell(CSC)/aldehyde dehydrogenase 1A1(ALDH1A1)/dendritic cell(DC)/cytotoxic T lymphocyte(CTL)/nasopharyngeal carcinoma分类
医药卫生引用本文复制引用
谢云青,许扬梅,陈珊珊,林晓为,刘沁颖..ALDH1A1 mRNA负载树突状细胞疫苗体外诱导抗鼻咽癌干细胞免疫反应[J].中国肿瘤生物治疗杂志,2026,33(5):486-493,8.基金项目
福建省卫生健康委员会医学创新课题(2023CXA036) （2023CXA036）
福建省科技创新联合资金项目(2024Y9622) （2024Y9622）
