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:Moderate-intensity aerobic exercise training improves CD8(+) tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.
Moderate-intensity aerobic exercise training improves CD8(+) tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.
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有氧运动训练被认为可降低癌症死亡率,但其影响肿瘤发展的机制尚不明确。肿瘤可通过形成免疫抑制微环境及损害T细胞功能逃避免疫监视,而T细胞线粒体减少与功能受损相关。有氧训练可改善线粒体含量和功能。本研究在CT26结肠癌细胞接种前后对小鼠进行跑台训练,评估肿瘤缺氧、TIL浸润和效应功能及线粒体状态。训练减少肿瘤生长、改善生存并降低肿瘤缺氧;CD8阳性TIL浸润增加,干扰素γ和ATP生成增强,这些变化与T细胞线粒体损失减少相关。结果提示有氧训练部分通过改善CD8阳性TIL线粒体状态及效应功能抑制肿瘤生长。
Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest.
Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8 + TIL infiltration, IFN- and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8 + TIL effector function through an improvement in their mitochondrial content and function.
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