基于重编程的基因疗法促进体内抗肿瘤免疫力

IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Nature genetics Pub Date : 2024-10-10 DOI:10.1038/s41588-024-01956-8
Chiara Anania
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引用次数: 0

摘要

癌症免疫疗法可诱导肿瘤抗原特异性 T 淋巴细胞反应,从而杀死肿瘤细胞。树突状细胞,特别是传统的 1 型树突状细胞(cDC1s),在抗原呈递中起着至关重要的作用,因此是免疫疗法的重要细胞类型。通过转录因子 PU.1、IRF8 和 BATF2(PIB)将肿瘤细胞重编程为 cDC1 样细胞可导致体外 T 细胞的强力活化。Ascic 等人的研究表明,PIB 介导的 cDC1 重编程可触发抗肿瘤免疫,并阻碍黑色素瘤小鼠模型中的肿瘤生长。此外,它还通过增加记忆和干样 T 细胞浸润,同时减少衰竭的 T 细胞数量来重塑肿瘤微环境。单细胞转录组学显示 CD4+ T 细胞群扩大,支持 PIB 介导的免疫。在所测试的基因治疗递送策略中,腺病毒载体显示出强大的肿瘤转导能力和原位重编程能力,能在淋巴结和肿瘤中引发高效的 T 细胞反应。因此,小鼠仍然没有肿瘤,并能抵抗转移扩散。重要的是,PIB 在人类异种移植和肿瘤球体内的过表达也能诱导 cDC1 重编程和免疫原性,而不受免疫抑制的影响。这项研究介绍了一种基于 cDC1 重编程的基因治疗方法,可促进长期、安全和高效的抗肿瘤免疫:科学 https://doi.org/10.1126/science.adn9083 (2024)
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Reprogramming-based gene therapy promotes anti-tumor immunity in vivo
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来源期刊
Nature genetics
Nature genetics 生物-遗传学
CiteScore
43.00
自引率
2.60%
发文量
241
审稿时长
3 months
期刊介绍: Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human and plant traits and on other model organisms. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation. Integrative genetic topics comprise, but are not limited to: -Genes in the pathology of human disease -Molecular analysis of simple and complex genetic traits -Cancer genetics -Agricultural genomics -Developmental genetics -Regulatory variation in gene expression -Strategies and technologies for extracting function from genomic data -Pharmacological genomics -Genome evolution
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