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:Role of the ITAM-Bearing Receptors Expressed by Natural Killer Cells in Cancer.
Role of the ITAM-Bearing Receptors Expressed by Natural Killer Cells in Cancer.
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自然杀伤(NK)细胞是先天淋巴样细胞(ILC),能够识别并直接杀伤肿瘤细胞。它们还分泌细胞因子和趋化因子,参与塑造适应性免疫应答。NK细胞识别肿瘤细胞,并通过抑制性受体和激活性受体的净正信号被激活。若干激活性NK细胞受体与含有免疫受体酪氨酸基激活基序(ITAM)的衔接分子偶联。这些受体包括CD16以及人类中的自然细胞毒性受体NKp46、NKp44、NKp30。这些激活性受体所触发的强大抗肿瘤NK细胞应答,使其成为免疫治疗中极具吸引力的靶点。在本综述中,我们将讨论NK细胞上表达的与含ITAM的细胞表面受体相关的不同激活性受体、它们在肿瘤环境中的调控,以及为增强癌症患者NK细胞应答而开发的各种治疗工具。
Natural Killer (NK) cells are innate lymphoid cells (ILCs) capable of recognizing and directly killing tumor cells. They also secrete cytokines and chemokines, which participate in the shaping of the adaptive response. NK cells identify tumor cells and are activated through a net positive signal from inhibitory and activating receptors. Several activating NK cell receptors are coupled to adaptor molecules containing an immunoreceptor tyrosine-based activation motif (ITAM).
These receptors include CD16 and the natural cytotoxic receptors NKp46, NKp44, NKp30 in humans. The powerful antitumor NK cell response triggered by these activating receptors has made them attractive targets for exploitation in immunotherapy. In this review, we will discuss the different activating receptors associated with ITAM-bearing cell surface receptors expressed on NK cells, their modulations in the tumor context and the various therapeutic tools developed to boost NK cell responses in cancer patients.
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