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:The Dynamic Role of NK Cells in Liver Cancers: Role in HCC and HBV Associated HCC and Its Therapeutic Implications.
The Dynamic Role of NK Cells in Liver Cancers: Role in HCC and HBV Associated HCC and Its Therapeutic Implications.
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肝细胞癌(HCC)仍是慢性肝病的重要并发症,尤其常见于肝硬化患者。现有治疗策略包括手术、局部区域治疗和化疗。NK 细胞是具有独特细胞毒性的淋巴细胞,在对抗肿瘤和感染中发挥重要作用。作为抗癌先天免疫系统的重要组成,HCC 患者 NK 细胞的表型和功能异常已有报道,且 NK 细胞活化受体/配体轴也发生紊乱。肿瘤浸润和循环 NK 细胞的比例与 HCC 生存获益呈正相关,并具有预后意义,提示 NK 细胞功能障碍与 HCC 进展密切相关。NK 细胞是病毒性肝炎的第一线效应细胞,可直接清除病毒感染细胞,或通过产生 IFN-γ 激活抗原特异性 T 细胞,从而发挥重要作用。
此外,嵌合抗原受体(CAR)工程化 NK 细胞提供了独特机会,可制备具有多种特异性的 CAR-NK,并减少副作用。本文综述肝脏先天免疫图景,特别是 NK 细胞,以及肿瘤免疫微环境(TIME)对 NK 细胞功能和 HCC 生物学特征的影响;并全面阐述 NK 细胞在 HCC 和 HBV 诱导 HCC 中的作用。本文还介绍 HCC 可用的 NK 细胞免疫治疗策略,并总结当前治疗进展,以帮助研究者理解 NK 细胞先天免疫环境的重要性,进而设计创新免疫疗法用于系统性治疗 HCC。
Hepatocellular carcinoma (HCC) remains an important complication of chronic liver disease, especially when cirrhosis occurs. Existing treatment strategies include surgery, loco-regional techniques, and chemotherapy. Natural killer cells are distinctive cytotoxic lymphocytes that play a vital role in fighting tumors and infections. As an important constituent of the innate immune system against cancer, phenotypic and functional deviations of NK cells have been demonstrated in HCC patients who also exhibit perturbation of the NK-activating receptor/ligand axis.
The rate of recurrence of tumor-infiltrating and circulating NK cells are positively associated with survival benefits in HCC and have prognostic significance, suggesting that NK cell dysfunction is closely related to HCC progression. NK cells are the first-line effector cells of viral hepatitis and play a significant role by directly clearing virus-infected cells or by activating antigen-specific T cells by producing IFN- .
In addition, chimeric antigen receptor (CAR) engineered NK cells suggest an exclusive opportunity to produce CAR-NKs with several specificities with fewer side effects. In the present review, we comprehensively discuss the innate immune landscape of the liver, particularly NK cells, and the impact of tumor immune microenvironment (TIME) on the function of NK cells and the biological function of HCC.
Furthermore, the role of NK cells in HCC and HBV-induced HCC has also been comprehensively elaborated.
We also elaborate on available NK cell-based immunotherapeutic approaches in HCC treatment and summarize current advancements in the treatment of HCC. This review will facilitate researchers to understand the importance of the innate immune landscape of NK cells and lead to devising innovative immunotherapeutic strategies for the systematic treatment of HCC.
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