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
一种具有抑制肿瘤生长和自身免疫潜力的免疫调节肽
英文原题：An immunomodulating peptide with potential to suppress tumour growth and autoimmunity.
查看英文原题
An immunomodulating peptide with potential to suppress tumour growth and autoimmunity.
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中文摘要
癌症和自身免疫性疾病常共存，而免疫检查点抑制剂治疗（ICI）会加剧自身免疫病理。我们最近描述了一种脂质肽，命名为IK14004，它促进免疫抑制性T调节（Treg）细胞的扩增，并在激活CD8+ T细胞的同时，将白细胞介素-2与干扰素-γ的产生解偶联。在此，我们报告IK14004介导的对Lewis肺癌（LLC）生长的抑制以及对脾细胞来源的耗竭CD4+ T细胞的再激活。在来自健康供者的人免疫细胞中，IK14004调节T细胞受体α/β亚基的表达，诱导I型IFN表达，刺激自然杀伤（NK）细胞表达NKG2D/NKp44受体并增强K562细胞毒性。在T细胞和NK细胞中，IK14004均改变IL-12受体β1/β2链比例，从而有利于IL-12p70结合。综上所述，这种新型肽为更深入了解ICI免疫治疗的复杂性提供了机会，从而可能在不促进肿瘤免疫逃逸的情况下将自身免疫反应降至最低。
展开英文摘要原文
Cancers and autoimmune diseases commonly co-exist and immune checkpoint inhibitor therapy (ICI) exacerbates autoimmune pathologies.
We recently described a lipidic peptide, designated IK14004, that promotes expansion of immunosuppressive T regulatory (Treg) cells and uncouples interleukin-2 from interferon-gamma production while activating CD8+ T cells.
Herein, we report IK14004-mediated inhibition of Lewis lung cancer (LLC) growth and re-invigoration of splenocyte-derived exhausted CD4+ T cells. In human immune cells from healthy donors, IK14004 modulates expression of the T cell receptor α/β subunits, induces Type I IFN expression, stimulates natural killer (NK) cells to express NKG2D/NKp44 receptors and enhances K562 cytotoxicity.
In both T and NK cells, IK14004 alters the IL-12 receptor β1/β2 chain ratio to favour IL-12p70 binding. Taken together, this novel peptide offers an opportunity to gain further insight into the complexity of ICI immunotherapy so that autoimmune responses may be minimised without promoting tumour evasion from the immune system.
论文信息
- 作者
- Agrez M、Chandler C、Thurecht KJ、Fletcher NL、Liu F、Subramaniam G、Howard CB、Blyth B
- 单位
- InterK Peptide Therapeutics Limited, New South Wales, Australia. michael.agrez@interk.com.au.Australia
- 期刊
- Scientific reports2023 Nov 13
- 原文标识
- PubMed 37957274 · DOI 10.1038/s41598-023-47229-y
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