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:Empowering γδ T-cell functionality with vitamin C.
Empowering γδ T-cell functionality with vitamin C.
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维生素C(抗坏血酸)是一种强效抗氧化剂,也是多种酶的辅因子,包括组蛋白去甲基化酶和甲基胞嘧啶双加氧酶。维生素C还对包括结直肠癌在内的部分肿瘤细胞具有直接细胞毒性。此外,维生素C已被证明在多个层面影响免疫细胞分化,包括T细胞及其祖细胞、树突状细胞、B细胞和NK细胞的成熟和/或功能。γδ T细胞由于能够以HLA非依赖的方式识别多种肿瘤细胞,近年来作为细胞癌症免疫治疗的效应细胞引起了极大关注。虽然γδ T细胞因此也可作为异体通用型产品应用,但显然需要优化γδ T细胞的效应功能以确保尽可能最佳的临床疗效。本文综述了维生素C的免疫调节机制,特别关注维生素C如何增强γδ T细胞的效应功能。我们还讨论了维生素C如何在临床环境中用于提升过继性细胞疗法疗效的未来方向。
Vitamin C (ascorbic acid) is a potent antioxidant and a cofactor for various enzymes including histone demethylases and methylcytosine dioxygenases. Vitamin C also exerts direct cytotoxicity toward selected tumor cells including colorectal carcinoma.
Moreover, vitamin C has been shown to impact immune cell differentiation at various levels including maturation and/or functionality of T cells and their progenitors, dendritic cells, B cells, and NK cells.
γδ T cells have recently attracted great interest as effector cells for cell-based cancer immunotherapy, due to their HLA-independent recognition of a large variety of tumor cells. While γδ T cells can thus be also applied as an allogeneic off-the-shelf product, it is obvious that the effector function of γδ T cells needs to be optimized to ensure the best possible clinical efficacy.
Here we review the immunomodulatory mechanisms of vitamin C with a special focus on how vitamin C enhances the effector function of γδ T cells.
We also discuss future directions of how vitamin C can be used in the clinical setting to boost the efficacy of adoptive cell therapies.
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