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:Analyzing the effect of NK cells on in-vivo models of tumor dissemination by digital pathology and flow cytometry.
Analyzing the effect of NK cells on in-vivo models of tumor dissemination by digital pathology and flow cytometry.
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尽管旨在生成复杂体外系统以重建3D组织及其自然灌注的研究显著扩展,但使用动物模型对于临床前测试免疫抗癌疗法的潜力仍然至关重要。考虑到肿瘤系统的异质性和复杂性,不断生成新的模型,以在小鼠或人类免疫环境存在下再现特定类型的原发性或转移性恶性肿瘤。这些模型适用于回答关于以下方面的特定问题:特定人类免疫细胞亚群在控制原发性肿瘤生长或转移扩散中的有效性,免疫浸润和肿瘤微环境的影响,以及参与肿瘤细胞识别或免疫抑制的关键分子的相关性。在本章中,我们介绍了NSG小鼠中人类非小细胞肺癌(NSCLC)的模型,这些小鼠缺乏成熟的B、T和NK细胞,是输注和研究人类免疫细胞(包括NK细胞)的最佳受体。我们特别描述了数字病理学和流式细胞术的分析方法,以表征和量化肿瘤形成的播散,以及外源性NK细胞在肿瘤组织浸润和控制肿瘤生长与扩散方面的活性。
Despite the significant expansion of the studies aimed at generating sophisticated in vitro systems to recreate 3D tissues and their natural perfusion, the use of animal models is still crucial to preclinically test the potential of immune-based anti-cancer therapies. Considering heterogeneity and complexity of the tumor systems, new models are continuously generated, to reproduce specific types of primary or metastatic malignancies, in the presence of murine or human immune environment. These models are adapted to answer peculiar questions regarding: the effectiveness of specific human immune cell subsets in controlling primary tumor growth or metastasis diffusion, the immune infiltration and the effects of tumor microenvironment, and, also, the relevance of key molecules involved in tumor cell recognition or immune suppression.
In this chapter we present a model of human Non-small cell lung cancer (NSCLC) in NSG mice, which lack mature B, T, and NK cells, and are optimal recipient for the infusion and the study of human immune cells, including NK cells. In particular we describe analytical approaches of digital pathology and flow cytometry to characterize and quantify the dissemination of the tumor formations, and the activity of exogenous NK cells in terms of infiltration of the tumor tissue and control of tumor growth and spread.
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