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:Adaptive NK Cells Exhibit Tumor-Specific Immune Memory and Cytotoxicity in Ovarian Cancer.
Adaptive NK Cells Exhibit Tumor-Specific Immune Memory and Cytotoxicity in Ovarian Cancer.
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适应性NK(aNK)细胞已作为一类具有记忆样特性和特异性细胞毒性的NK细胞亚群出现,在肿瘤免疫治疗中展现出有前景的治疗潜力。在本研究中,我们探索了aNK细胞在高grade浆液性卵巢癌中的作用,重点关注其建立肿瘤特异性免疫记忆并有效靶向自体肿瘤的能力。通过结合in silico、in vitro和ex vivo方法,我们证明aNK细胞与传统NK细胞不同,表现出回忆应答、特异性细胞毒性以及优先浸润至肿瘤微环境。我们的数据揭示,aNK细胞通过HLA-E/NKG2C轴和CXCR2信号与肿瘤微环境中的树突状细胞相互作用,促进其记忆形成和肿瘤靶向能力。这些发现表明,aNK细胞可作为基于NK细胞的免疫治疗中的强效制剂,尤其是在高grade浆液性卵巢癌等实体瘤中,它们能够抵抗免疫抑制信号并维持强健的抗肿瘤活性。本研究为aNK细胞的适应性样特性提供了新的见解,强调了其在推进癌症免疫治疗策略方面的潜力。
Adaptive NK (aNK) cells have emerged as a subset of NK cells with memory-like properties and specific cytotoxicity, offering promising therapeutic potential in cancer immunotherapy. In this study, we explored the role of aNK cells in high-grade serous ovarian cancer, focusing on their ability to establish tumor-specific immune memory and effectively target autologous tumors.
Through a combination of in silico, in vitro, and ex vivo approaches, we demonstrated that aNK cells, in contrast to conventional NK cells, exhibit recall responses, specific cytotoxicity, and preferential infiltration into the tumor microenvironment.
Our data revealed that aNK cells interact with dendritic cells within the tumor microenvironment via the HLA-E/NKG2C axis and CXCR2 signaling, contributing to their memory formation and tumor-targeting capabilities.
These findings suggest that aNK cells could serve as potent agents in NK cell-based immunotherapies, particularly in solid tumors such as high-grade serous ovarian cancer, in which they resist immunosuppressive signals and maintain robust antitumor activity.
This study provides new insights into the adaptive-like properties of aNK cells, underscoring their potential for advancing cancer immunotherapy strategies.
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