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:The Impact of Metformin on Tumor-Infiltrated Immune Cells: Preclinical and Clinical Studies.
The Impact of Metformin on Tumor-Infiltrated Immune Cells: Preclinical and Clinical Studies.
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肿瘤微环境(TME)在癌细胞的命运中起着关键作用,而肿瘤浸润免疫细胞已成为塑造这一复杂环境的关键参与者。癌症是世界上主要的死亡原因之一。最常见的癌症标准治疗方法是手术、放射治疗和化疗药物。在过去十年中,免疫治疗对预后较差的癌症患者的治疗产生了潜在影响。一种显示出抗癌疗效的免疫治疗靶向方法是2型糖尿病药物二甲双胍。除了其血糖控制特性外,研究还揭示了二甲双胍有趣的免疫调节特性。
同时,多项研究关注二甲双胍在各种肿瘤模型中对肿瘤浸润免疫细胞的影响。在多种肿瘤模型中,二甲双胍可以调节肿瘤浸润的效应免疫细胞、CD8+、CD4+ T细胞和自然杀伤(NK)细胞,以及抑制性免疫细胞、T调节细胞、肿瘤相关巨噬细胞(TAMs)和髓源性抑制细胞(MDSCs)。在这篇综述中,我们讨论了二甲双胍在不同临床前模型和临床试验中调节肿瘤浸润免疫细胞的作用。临床前和临床研究均表明,二甲双胍通过调节肿瘤微环境中的免疫反应,有望成为癌症治疗的辅助疗法。尽管如此,肿瘤类型和联合治疗均会影响二甲双胍在TME中的特定靶点。需要进一步研究以阐明二甲双胍免疫调节作用的确切机制,并优化其在癌症患者中的临床应用。
The tumor microenvironment (TME) plays a pivotal role in the fate of cancer cells, and tumor-infiltrating immune cells have emerged as key players in shaping this complex milieu. Cancer is one of the leading causes of death in the world. The most common standard treatments for cancer are surgery, radiation therapy, and chemotherapeutic drugs. In the last decade, immunotherapy has had a potential effect on the treatment of cancer patients with poor prognoses. One of the immune therapeutic targeted approaches that shows anticancer efficacy is a type 2 diabetes medication, metformin. Beyond its glycemic control properties, studies have revealed intriguing immunomodulatory properties of metformin. Meanwhile, several studies focus on the impact of metformin on tumor-infiltrating immune cells in various tumor models.
In several tumor models, metformin can modulate tumor-infiltrated effector immune cells, CD8 + , CD4 + T cells, and natural killer (NK) cells, as well as suppressor immune cells, T regulatory cells, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs). In this review, we discuss the role of metformin in modulating tumor-infiltrating immune cells in different preclinical models and clinical trials.
Both preclinical and clinical studies suggest that metformin holds promise as adjunctive therapy in cancer treatment by modulating the immune response within the tumor microenvironment. Nonetheless, both the tumor type and the combined therapy have an impact on the specific targets of metformin in the TME.
Further investigations are warranted to elucidate the precise mechanisms underlying the immunomodulatory effects of metformin and to optimize its clinical application in cancer patients.
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