CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
效应 T 细胞中 SOCS3 缺失赋予 IL-6 抗肿瘤作用，使其从促肿瘤细胞因子转变为抗肿瘤细胞因子
英文原题：SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine.
查看英文原题
SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine.
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中文摘要
白细胞介素（IL）-6在肿瘤微环境中大量表达，并与患者不良预后相关。在此，我们证明，在小鼠和人类模型中，T细胞中细胞因子信号传导抑制因子3（SOCS3）的缺失通过赋予IL-6抗肿瘤功能来增强抗肿瘤免疫应答。在Socs3缺陷的CD8+ T细胞中，IL-6上调I型干扰素（IFN）调节基因的表达，并增强T细胞的抗肿瘤效应功能，同时还改变线粒体适应性，以提高线粒体膜电位和活性氧（ROS）水平，并在能量状态下促进代谢糖酵解。此外，Socs3缺陷减少调节性T细胞并增加辅助性T细胞1（Th1）细胞。在人源化小鼠中，人CAR-T（CAR-T）细胞中SOCS3敲低表现出强烈的抗肿瘤反应。因此，SOCS3的基因破坏为提高过继性T细胞疗法的治疗效果提供了一条途径。
展开英文摘要原文
Interleukin (IL)-6 is abundantly expressed in the tumor microenvironment and is associated with poor patient outcomes.
Here, we demonstrate that the deletion of the suppressor of cytokine signaling 3 (SOCS3) in T cells potentiates anti-tumor immune responses by conferring the anti-tumorigenic function of IL-6 in mouse and human models.
In Socs3-deficient CD8 + T cells, IL-6 upregulates the expression of type I interferon (IFN)-regulated genes and enhances the anti-tumor effector function of T cells, while also modifying mitochondrial fitness to increase mitochondrial membrane potential and reactive oxygen species (ROS) levels and to promote metabolic glycolysis in the energy state.
Furthermore, Socs3 deficiency reduces regulatory T cells and increases T helper 1 (Th1) cells. SOCS3 knockdown in human chimeric antigen receptor T (CAR-T) cells exhibits a strong anti-tumor response in humanized mice.
Thus, genetic disruption of SOCS3 offers an avenue to improve the therapeutic efficacy of adoptive T cell therapy.
论文信息
- 作者
- Mise-Omata S、Ando M、Srirat T、Nakagawara K、Hayakawa T、Iizuka-Koga M、Nishimasu H、Nureki O
- 第一作者单位
- Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. Electronic address: setsukomise@gmail.com.Japan
- 通讯作者单位
- Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. Electronic address: yoshimura@keio.jp.Japan
- 文献类型
- 非美国政府资助研究
- 期刊
- Cell reports2023 Aug 29
- 原文标识
- PubMed 37582370 · DOI 10.1016/j.celrep.2023.112940