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 importance of immune checkpoints in immune monitoring: A future paradigm shift in the treatment of cancer.
The importance of immune checkpoints in immune monitoring: A future paradigm shift in the treatment of cancer.
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癌症的生长和发育与免疫系统的抑制直接相关。癌症免疫治疗的一项重大突破依赖于多种机制来检测抑制抗肿瘤免疫反应的免疫抑制因子。免疫检查点在许多免疫细胞上表达,如T细胞、调节性B细胞(Bregs)、树突状细胞(DCs)、NK 细胞(NKs)、调节性T细胞(Tregs)、M2型巨噬细胞和髓源性抑制细胞(MDSCs)。免疫抑制分子,包括CTLA-4、TIM-3、TIGIT、PD-1和LAG-3,通常通过负向调节免疫细胞信号通路来抑制免疫反应,以防止免疫损伤。
然而,在肿瘤进展过程中,免疫细胞上抑制性免疫检查点的上调会抑制抗肿瘤免疫反应并促进癌症的免疫逃逸。最近有研究表明,癌细胞可以上调免疫检查点的多种通路。
因此,通过抗体或miRNAs靶向免疫抑制分子是一种有前景的治疗策略,并显示出良好的结果。免疫检查点抑制剂(ICIs)作为一种新的免疫治疗策略被引入,可增强免疫细胞诱导的抗肿瘤反应,使许多患者获益。在这篇综述中,我们重点介绍了每个免疫检查点在不同免疫细胞上的功能,以及旨在使用单克隆抗体和miRNAs针对抑制性受体的治疗策略。
我们还讨论了当前面临的挑战以及未来策略,以最大化这些FDA批准的免疫抑制剂在癌症治疗中的有效性和临床成功率。
The growth and development of cancer are directly correlated to the suppression of the immune system. A major breakthrough in cancer immunotherapy depends on various mechanisms to detect immunosuppressive factors that inhibit anti-tumor immune responses.
Immune checkpoints are expressed on many immune cells such as T-cells, regulatory B cells (Bregs), dendritic cells (DCs), natural killer cells (NKs), regulatory T (Tregs), M2-type macrophages, and myeloid-derived suppressor cells (MDSCs). Immune inhibitory molecules, including CTLA-4, TIM-3, TIGIT, PD-1, and LAG-3, normally inhibit immune responses via negatively regulating immune cell signaling pathways to prevent immune injury.
However, the up-regulation of inhibitory immune checkpoints during tumor progression on immune cells suppresses anti-tumor immune responses and promotes immune escape in cancer. It has recently been indicated that cancer cells can up-regulate various pathways of the immune checkpoints.
Therefore, targeting immune inhibitory molecules through antibodies or miRNAs is a promising therapeutic strategy and shows favorable results. Immune checkpoint inhibitors (ICIs) are introduced as a new immunotherapy strategy that enhance immune cell-induced antitumor responses in many patients. In this review, we highlighted the function of each immune checkpoint on different immune cells and therapeutic strategies aimed at using monoclonal antibodies and miRNAs against inhibitory receptors.
We also discussed current challenges and future strategies for maximizing these FDA-approved immunosuppressants' effectiveness and clinical success in cancer treatment.
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