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:Cancer Therapy Targeting CD47/SIRPα.
Cancer Therapy Targeting CD47/SIRPα.
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在过去十年中,肿瘤免疫治疗领域迅速发展,确立了免疫检查点阻断剂在多种癌症类型治疗中的关键作用。与这些显著的临床进展并行,进一步的研究致力于释放针对癌症的适应性免疫反应。CD47是一种细胞表面分子,在多种癌症类型中过表达,促进免疫逃逸,逃避巨噬细胞、树突状细胞和NK 细胞的攻击,其配体SIRPα已成为潜在的治疗靶点。针对CD47/SIRPα的多种药物已被开发并显示出临床前活性。早期临床试验正在研究针对CD47/SIRPα的药物,现有数据表明其安全性和初步活性。在此,我们概述了靶向CD47/SIRPα轴的机制原理及相关临床证据。
In the past decade, the field of cancer immunotherapy has rapidly advanced, establishing a crucial role for immune checkpoint blockers in the treatment of a variety of cancer types. In parallel with these remarkable clinical developments, further efforts have focused on ways of unleashing adaptive immune responses against cancer.
CD47, a cell surface molecule overexpressed by several cancer types that facilitates immune escape from macrophages, dendritic cells and natural killer cells, and its ligand SIRPα, have emerged as potential therapeutic targets. A number of agents directed to CD47/SIRPα have been developed and demonstrated preclinical activity. Early phase clinical trials are investigating CD47/SIRPα directed agents with available data, suggesting safety and preliminary activity.
Herein, we provide an overview of the mechanistic rationale of targeting CD47/SIRPα axis and associated clinical evidence.
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