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:Thymic NK-Cells and Their Potential in Cancer Immunotherapy.
Thymic NK-Cells and Their Potential in Cancer Immunotherapy.
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自然杀伤(NK)细胞是具有强大抗肿瘤能力的先天免疫细胞,无需预先接触即可识别靶细胞,因此被视为细胞治疗的有用来源。多数NK细胞来源于骨髓(BM),但胸腺中也存在另一条发育途径,可产生所谓胸腺NK细胞。与常规NK细胞不同,胸腺NK(tNK)细胞兼具细胞因子生成能力,并能在存在NK细胞受体刺激性配体时天然杀伤肿瘤细胞。此外,据报道,tNK细胞在细胞内表达CD3亚基,却不存在重排后的T细胞受体(TCR)。这一独特特征可能使其能够与TCR结合应用,从而在一种细胞类型中整合NK和T细胞效应功能。然而,目前对tNK细胞的发育、表型和功能及其作为细胞疗法的潜力研究有限。本文综述小鼠和人tNK细胞的现有文献,并将其与常规骨髓来源NK细胞进行比较,同时讨论该细胞亚群在癌症免疫治疗中的潜在应用。
Natural killer (NK)-cells are innate immune cells with potent anti-tumor capacity, capable of recognizing target cells without prior exposure. For this reason, NK-cells are recognized as a useful source of cell therapy.
Although most NK-cells are derived from the bone marrow (BM), a separate developmental pathway in the thymus also exists, producing so-called thymic NK-cells. Unlike conventional NK-cells, thymic NK (tNK)-cells have a combined capacity for cytokine production and a natural ability to kill tumor cells in the presence of NK-cell receptor stimulatory ligands.
Furthermore, tNK-cells are reported to express CD3 subunits intracellularly, without the presence of a rearranged T-cell receptor (TCR). This unique feature may enable harnessing of these cells with a TCR to combine NK- and T-cell effector properties in one cell type.
The development, phenotype, and function of tNK-cells, and potential as a cell therapy is, however, poorly explored. In this review, we provide an overview of current literature on both murine and human tNK-cells in comparison to conventional BM-derived NK-cells, and discuss the potential applications of this cellular subset in the context of cancer immunotherapy.
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