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:ADCC: the rock band led by therapeutic antibodies, tumor and immune cells.
ADCC: the rock band led by therapeutic antibodies, tumor and immune cells.
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抗体依赖性细胞介导的细胞毒性(ADCC)是治疗性抗体利用免疫系统靶向和消灭癌细胞的关键机制。ADCC的主要效应细胞是自然杀伤(NK)细胞,其通过CD16受体特异性靶向被抗体覆盖的癌细胞。虽然其他免疫细胞和Fc受体也能参与并增强ADCC,但NK细胞和CD16受体对于曲妥珠单抗、西妥昔单抗和利妥昔单抗等癌症疗法的疗效至关重要。共培养实验对于理解这些疗法的机制、克服耐药性以及优化新型治疗性抗体至关重要。本综述强调了测量ADCC以评估治疗性抗体疗效的重要性。
在此,我们还介绍了可用于研究ADCC的各种体外模型和实验方法,比较了使用PBMC以更好地反映真实条件与使用NK细胞系以实现标准化等方法各自的优势和局限性。本综述还涵盖了ADCC的不同检测指标,包括聚焦于效应细胞活化的检测,如报告基因实验和脱颗粒实验,以及聚焦于靶细胞杀伤的检测,如不同的分子释放实验、流式细胞术和免疫荧光技术。选择最佳模型来研究ADCC对于治疗性抗体研究的转化意义至关重要。
Antibody-dependent cellular cytotoxicity (ADCC) is a critical mechanism by which therapeutic antibodies leverage the immune system to target and eliminate cancer cells. The key agents of ADCC are natural killer (NK) cells, specifically targeting antibody-covered cancer cells through the CD16 receptor.
While other immune cells and Fc receptors can contribute and enhance ADCC, NK cells and the CD16 receptor are crucial for the efficacy of cancer therapies such as trastuzumab, cetuximab and rituximab. Co-culture assays are essential for understanding the mechanisms of these therapies, overcoming resistance and optimizing novel therapeutic antibodies. This review highlights the importance of measuring ADCC to assess the efficacy of therapeutic antibodies.
Here we also present the various in vitro models and assay methodologies available for studying ADCC, comparing the strengths and limitations of approaches like using PBMCs to better reflect real-life conditions or NK cell lines for standardization.
It also covers different readouts for ADCC, either focusing on effector cells activation, including reporter and degranulation assays or in the target cell killing, including different molecule release assays, flow cytometry and immunofluorescence techniques. Selecting the best model for studying ADCC is crucial for the translational significance of therapeutic antibody research.
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