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 NKT cells in cancer immunotherapy-from bench to bed.
Role of NKT cells in cancer immunotherapy-from bench to bed.
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自然杀伤T(NKT)细胞是一类特殊T细胞亚群,表达用于抗原识别的T细胞受体(TCR),并具有典型NK细胞特征,如表面表达CD56和CD16标志物及产生颗粒酶。根据细胞因子受体和TCR库,人体NKT细胞分为两个亚群。两者均受CD1限制,并识别由CD1d分子呈递的脂质抗原。研究显示,这些细胞对于防御恶性肿瘤至关重要。它们分泌促炎和调节性细胞因子,可刺激或抑制免疫系统应答。在多种小鼠肿瘤模型中,激活I型NKT细胞可诱导肿瘤排斥并抑制转移扩散;而II型NKT细胞在肿瘤免疫应答中具有抑制和调节功能。变异型NKT细胞可通过与其他免疫调节细胞的相互作用机制抑制抗肿瘤免疫。类NKT细胞对多种肿瘤细胞具有很强的杀伤能力。近十年来,研究者开展了多项NKT细胞免疫治疗癌症的研究。
此外,也测试了通过给予负载α-半乳糖基神经酰胺(α-GalCer)的自体树突状细胞(DC)以及直接注射α-GalCer来调节NKT细胞的策略。本文综述NKT细胞的不同亚型、其在抗肿瘤免疫应答中的功能,以及NKT细胞从基础研究到临床应用于癌症免疫治疗的进展。
Natural killer T (NKT) cells are a specific T cell subset known to express the -T cell receptor (TCR) for antigens identification and express typical NK cell specifications, such as surface expression of CD56 and CD16 markers as well as production of granzyme. Human NKT cells are divided into two subgroups based on their cytokine receptor and TCR repertoire.
Both of them are CD1-restricted and recognize lipid antigens presented by CD1d molecules. Studies have demonstrated that these cells are essential in defense against malignancies. These cells secret proinflammatory and regulatory cytokines that stimulate or suppress immune system responses. In several murine tumor models, activation of type I NKT cells induces tumor rejection and inhibits metastasis's spread.
However, type II NKT cells are associated with an inhibitory and regulatory function during tumor immune responses. Variant NKT cells may suppress tumor immunity via different mechanisms that require cross-talk with other immune-regulatory cells. NKT-like cells display high tumor-killing abilities against many tumor cells. In the recent decade, different studies have been performed based on the application of NKT-based immunotherapy for cancer therapy.
Moreover, manipulation of NKT cells through administering autologous dendritic cell (DC) loaded with -galactosylceramide ( -GalCer) and direct -GalCer injection has also been tested. In this review, we described different subtypes of NKT cells, their function in the anti-tumor immune responses, and the application of NKT cells in cancer immunotherapy from bench to bed.
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