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引用次数: 0
摘要
自然杀伤(NK)细胞是先天性免疫防御中最重要的细胞之一。与 T 细胞相比,NK 细胞的效应功能不需要事先刺激,也不受 MHC 限制。因此,嵌合抗原受体(CAR)-NK 细胞优于 CAR-T 细胞。肿瘤微环境(TME)的复杂性使得有必要探索 NK 细胞负调控的各种途径。通过抑制负调控机制,可以改善 CAR-NK 细胞的效应功能。在这方面,已知 E3 泛素连接酶含三方基序 29(TRIM29)参与降低 NK 细胞的细胞毒性和细胞因子的产生。此外,靶向 TRIM29 可能会增强 CAR-NK 细胞的抗肿瘤功效。本研究讨论了 TRIM29 对 NK 细胞活性的负面影响,并提出基因组删除或抑制 TRIM29 的表达是优化基于 CAR-NK 细胞的免疫疗法的一种新方法。
Targeting TRIM29 As a Negative Regulator of CAR-NK Cell Effector Function to Improve Antitumor Efficacy of these Cells: A Perspective.
Natural killer (NK) cells are among the most important cells in innate immune defense. In contrast to T cells, the effector function of NK cells does not require prior stimulation and is not MHC restricted. Therefore, chimeric antigen receptor (CAR)-NK cells are superior to CAR-T cells. The complexity of the tumor microenvironment (TME) makes it necessary to explore various pathways involved in NK cell negative regulation. CAR-NK cell effector function can be improved by inhibiting the negative regulatory mechanisms. In this respect, the E3 ubiquitin ligase tripartite motif containing 29 (TRIM29) is known to be involved in reducing NK cell cytotoxicity and cytokine production. Also, targeting TRIM29 may enhance the antitumor efficacy of CAR-NK cells. The present study discusses the negative effects of TRIM29 on NK cell activity and proposes genomic deletion or suppression of the expression of TRIM29 as a novel approach to optimize CAR-NK cell-based immunotherapy.
期刊介绍:
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.