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
英文原题:Advancements in CRISPR screens for the development of cancer immunotherapy strategies.
Advancements in CRISPR screens for the development of cancer immunotherapy strategies.
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CRISPR筛选技术利用CRISPR-Cas9系统扰动基因表达,可系统且大规模地解析基因功能。在癌症免疫治疗领域,该技术推动发现调节肿瘤发生和进展、免疫反应性及免疫治疗干预效果的基因、生物标志物和通路。通过大规模遗传筛选,研究人员已成功发现可抑制肿瘤生长、增强抗肿瘤免疫应答并克服肿瘤微环境(TME)免疫抑制的新靶点。本文综述在肿瘤细胞中开展的CRISPR筛选及其发现新治疗靶点的应用,并探讨在免疫细胞中开展CRISPR筛选、推动细胞疗法发展的用途,包括T细胞、NK 细胞、树突状细胞和巨噬细胞。此外,文章概述成功开展免疫细胞特异性CRISPR筛选所需的关键要素,并探讨未来研究方向。
CRISPR screen technology enables systematic and scalable interrogation of gene function by using the CRISPR-Cas9 system to perturb gene expression. In the field of cancer immunotherapy, this technology has empowered the discovery of genes, biomarkers, and pathways that regulate tumor development and progression, immune reactivity, and the effectiveness of immunotherapeutic interventions.
By conducting large-scale genetic screens, researchers have successfully identified novel targets to impede tumor growth, enhance anti-tumor immune responses, and surmount immunosuppression within the tumor microenvironment (TME).
Here, we present an overview of CRISPR screens conducted in tumor cells for the purpose of identifying novel therapeutic targets.
We also explore the application of CRISPR screens in immune cells to propel the advancement of cell-based therapies, encompassing T cells, natural killer cells, dendritic cells, and macrophages.
Furthermore, we outline the crucial components necessary for the successful implementation of immune-specific CRISPR screens and explore potential directions for future research.
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