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:Ultrasound-targeted microbubble destruction remodels tumour microenvironment to improve immunotherapeutic effect.
Ultrasound-targeted microbubble destruction remodels tumour microenvironment to improve immunotherapeutic effect.
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肿瘤免疫治疗(CIT)近年来受到越来越多的关注并取得了令人鼓舞的进展,尤其是免疫检查点抑制剂,如阻断程序性细胞死亡1/程序性细胞死亡配体1(PD-1/PD-L1)和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)的抗体。
然而,其在实体瘤中的治疗效果仅为10-30%,治疗敏感性有待提高。癌症发生的复杂组织环境被称为肿瘤微环境(TME),复杂且动态的TME与免疫治疗的疗效相关。超声靶向微泡破坏(UTMD)是一项集诊断与治疗于一体的新兴技术,因其非侵入性、靶向药物递送和基因转染特性而备受关注。UTMD也已被研究用于重塑TME并提高CIT的疗效。在本综述中,我们分析了UTMD对TME各组分的影响,包括CD8+ T细胞、肿瘤浸润髓系细胞、调节性T细胞、NK 细胞和肿瘤血管系统。
此外,UTMD可增强血脑屏障的通透性以促进药物递送,从而在体内动物实验中提高CIT疗效。基于此,我们重点阐述了免疫治疗针对多种癌症类型的潜力以及UTMD的临床应用前景。
Cancer immunotherapy (CIT) has gained increasing attention and made promising progress in recent years, especially immune checkpoint inhibitors such as antibodies blocking programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4).
However, its therapeutic efficacy is only 10-30% in solid tumours and treatment sensitivity needs to be improved. The complex tissue environment in which cancers originate is known as the tumour microenvironment (TME) and the complicated and dynamic TME is correlated with the efficacy of immunotherapy.
Ultrasound-targeted microbubble destruction (UTMD) is an emerging technology that integrates diagnosis and therapy, which has garnered much traction due to non-invasive, targeted drug delivery and gene transfection characteristics. UTMD has also been studied to remodel TME and improve the efficacy of CIT. In this review, we analyse the effects of UTMD on various components of TME, including CD8 + T cells, tumour-infiltrating myeloid cells, regulatory T cells, natural killer cells and tumour vasculature.
Moreover, UTMD enhances the permeability of the blood-brain barrier to facilitate drug delivery, thus improving CIT efficacy in vivo animal experiments. Based on this, we highlight the potential of immunotherapy against various cancer species and the clinical application prospects of UTMD.
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