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:LLT1-CD161 Interaction in Cancer: Promises and Challenges.
LLT1-CD161 Interaction in Cancer: Promises and Challenges.
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免疫检查点疗法在癌症治疗中的成功改变了我们的思维方式,推动了以免疫系统为核心舞台的未来癌症治疗设计。在免疫调节和耐受方面获得的知识有助于识别有前景的新临床免疫靶点。其中,凝集素样转录本1(LLT1)是NK 细胞和T细胞上表达的CD161(NKR-P1A)受体的配体。LLT1/CD161相互作用调节免疫应答,但所传递信号的确切性质仍部分未解。由于动物模型中缺乏功能性同源物,对LLT1/CD161相互作用作用的研究受到阻碍。此外,一些研究因使用非特异性试剂而被误导。近期研究和单细胞数据的荟萃分析正在为LLT1和CD161在人类病理学尤其是癌症中的功能带来新见解。肿瘤微环境表征方面的进展促使我们将LLT1/CD161相互作用纳入考量。本综述概述了关于LLT1和CD161表达谱、其调控、它们相互作用在癌症发展中的作用以及靶向LLT1/CD161相互作用相关性的关键发现。
The success of immune checkpoint therapy in cancer has changed our way of thinking, promoting the design of future cancer treatments that places the immune system at the center stage. The knowledge gained on immune regulation and tolerance helped the identification of promising new clinical immune targets. Among them, the lectin-like transcript 1 (LLT1) is the ligand of CD161 (NKR-P1A) receptor expressed on natural killer cells and T cells. LLT1/CD161 interaction modulates immune responses but the exact nature of the signals delivered is still partially resolved. Investigation on the role of LLT1/CD161 interaction has been hampered by the lack of functional homologues in animal models.
Also, some studies have been misled by the use of non-specific reagents. Recent studies and meta-analyses of single cell data are bringing new insights into the function of LLT1 and CD161 in human pathology and notably in cancer.
The advances made on the characterization of the tumor microenvironment prompt us to integrate LLT1/CD161 interaction into the equation. This review recapitulates the key findings on the expression profile of LLT1 and CD161, their regulation, the role of their interaction in cancer development, and the relevance of targeting LLT1/CD161 interaction.
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