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:Targeting immune checkpoint therapy: The role of manganese in tumor immunotherapy.
Targeting immune checkpoint therapy: The role of manganese in tumor immunotherapy.
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癌症免疫治疗已成为放疗和化疗等传统治疗的一种有前景的补充。尽管传统疗法仍是癌症管理的核心,但免疫治疗的潜力正日益受到认可。免疫检查点治疗作为肿瘤免疫治疗的关键策略,已显示出对实体瘤的显著疗效。
然而,其临床应用受到缓解率有限的制约,因此需要努力优化其疗效。近期研究强调了环鸟苷酸-腺苷酸合成酶(cGAS)-干扰素基因刺激因子(STING)通路在免疫检查点治疗中的关键作用。锰(Mn)作为一种必需微量元素,通过调节cGAS-STING通路来调控CD8+ T细胞和NK细胞的活性。
此外,Mn与抗程序性细胞死亡蛋白1治疗的联合已显示出有前景的抗肿瘤效果。Mn还影响免疫原性细胞死亡(ICD),进一步增强其作为肿瘤免疫治疗辅助手段的潜力。尽管关于Mn在调节cGAS-STING通路和诱导ICD中作用的研究日益增多,但综合这些发现并探索Mn在增强免疫检查点治疗中潜力的全面综述仍然缺乏。本综述旨在通过探讨Mn增强免疫检查点治疗的免疫机制及其对肿瘤免疫治疗的整体影响来填补这一空白。
Cancer immunotherapy has emerged as a promising complement to traditional treatments such as radiotherapy and chemotherapy. Although conventional therapies remain central to cancer management, the potential of immunotherapy is increasingly recognized. Immune checkpoint therapy, a key strategy in tumor immunotherapy, has demonstrated significant efficacy against solid tumors.
However, its clinical application is hindered by its limited response rate, necessitating efforts to optimize its effectiveness. Recent studies have highlighted the pivotal role of the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon gene (STING) pathway in immune checkpoint therapy. Manganese (Mn), an essential trace element, regulates the activity of CD8 + T and NK cells by modulating the cGAS-STING pathway.
Furthermore, the combination of Mn with anti-programmed cell death protein 1 therapy has demonstrated promising anti-tumor effects. Mn also influences immunogenic cell death (ICD), further augmenting its potential as an adjunct to tumor immunotherapy.
Despite a growing body of research on the role of Mn in modulating the cGAS-STING pathway and inducing ICD, comprehensive reviews that synthesize these findings and explore the potential of Mn in enhancing immune checkpoint therapy are still lacking. This review aimed to fill this gap by examining the immune mechanisms by which Mn enhances immune checkpoint therapy and its overall impact on tumor immunotherapy.
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