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
胆固醇调节的细胞刚度可能增强胃癌干细胞对 NK 细胞介导的细胞毒性的逃逸
英文原题：Cholesterol-regulated cellular stiffness may enhance evasion of NK cell-mediated cytotoxicity in gastric cancer stem cells.
查看英文原题
Cholesterol-regulated cellular stiffness may enhance evasion of NK cell-mediated cytotoxicity in gastric cancer stem cells.
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中文摘要
胃癌复发率高，因此免疫治疗策略正被研究作为潜在的治疗策略。尽管免疫检查点参与免疫治疗已被充分研究，但生物力学线索，如靶细胞硬度，尚未受到同等程度的研究。细胞膜胆固醇含量的变化直接影响肿瘤细胞硬度。在此，我们研究了胆固醇对NK细胞介导的胃癌干细胞样细胞杀伤的影响。我们报道，具有干细胞样特性的存活肿瘤细胞通过升高胆固醇代谢来逃避NK细胞细胞毒性。抑制胆固醇代谢可增强NK细胞介导的胃癌干细胞样细胞杀伤，突显了提高免疫治疗疗效的潜在途径。本研究提示癌细胞硬度对免疫逃逸的可能影响，并为增强针对肿瘤的免疫治疗策略提供了见解。
展开英文摘要原文
Gastric cancer has a high rate of recurrence, and as such, immunotherapy strategies are being investigated as a potential therapeutic strategy. Although the involvement of immune checkpoints in immunotherapy is well studied, biomechanical cues, such as target cell stiffness, have not yet been subject to the same level of investigation. Changes in the cholesterol content of the cell membrane directly influence tumor cell stiffness.
Here, we investigated the effect of cholesterol on NK cell-mediated killing of gastric cancer stem-like cells.
We report that surviving tumor cells with stem-like properties elevated cholesterol metabolism to evade NK cell cytotoxicity. Inhibition of cholesterol metabolism enhances NK cell-mediated killing of gastric cancer stem-like cells, highlighting a potential avenue for improving immunotherapy efficacy.
This study suggests a possible effect of cancer cell stiffness on immune evasion and offers insights into enhancing immunotherapeutic strategies against tumors.
论文信息
- 作者
- Zhu L、Wang H
- 第一作者单位
- Department of Radiation Oncology (II), The First Affiliated Hospital of Jinzhou Medical University, China.China
- 通讯作者单位
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinzhou Medical University, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- FEBS open bio2024 May
- 原文标识
- PubMed 38494433 · DOI 10.1002/2211-5463.13793
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