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
FTO 负向调节 NK 细胞的细胞毒性活性
英文原题：FTO negatively regulates the cytotoxic activity of natural killer cells.
查看英文原题
FTO negatively regulates the cytotoxic activity of natural killer cells.
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中文摘要
N6-甲基腺苷（m6A）是最丰富的表观转录组标记，在mRNA代谢的几乎每个方面都发挥着基础性作用。尽管m6A写入器和读取器已被广泛研究，但m6A擦除器的角色仍未得到充分理解。在此，我们研究了FTO——m6A擦除器之一——在自然杀伤（NK）细胞免疫中的作用。我们观察到FTO缺陷的NK细胞处于过度活化状态。Fto敲除（Fto-/-）小鼠NK细胞在体内阻止黑色素瘤转移，而FTO缺陷的人NK细胞在体外增强对白血病的抗肿瘤反应。我们发现FTO通过增加细胞因子信号传导抑制蛋白（SOCS）家族基因的mRNA稳定性，负向调控IL-2/15驱动的JAK/STAT信号传导。我们的结果表明，FTO是NK细胞免疫的重要调节因子，为同种异体NK细胞疗法提供了新的免疫治疗策略。
展开英文摘要原文
N 6 -Methyladenosine (m 6 A) is the most abundant epitranscriptomic mark and plays a fundamental role in almost every aspect of mRNA metabolism. Although m 6 A writers and readers have been widely studied, the roles of m 6 A erasers are not well-understood.
Here, we investigate the role of FTO, one of the m 6 A erasers, in natural killer (NK) cell immunity.
We observe that FTO-deficient NK cells are hyperactivated. Fto knockout (Fto -/- ) mouse NK cells prevent melanoma metastasis in vivo, and FTO-deficient human NK cells enhance the antitumor response against leukemia in vitro.
We find that FTO negatively regulates IL-2/15-driven JAK/STAT signaling by increasing the mRNA stability of suppressor of cytokine signaling protein (SOCS) family genes.
Our results suggest that FTO is an essential modulator of NK cell immunity, providing a new immunotherapeutic strategy for allogeneic NK cell therapies.
论文信息
- 作者
- Kim SM、Oh SC、Lee SY、Kong LZ、Lee JH、Kim TD
- 单位
- Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.South Korea
- 文献类型
- 非美国政府资助研究
- 期刊
- EMBO reports2023 Apr 5
- 原文标识
- PubMed 36744362 · DOI 10.15252/embr.202255681
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