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:Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas.
Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas.
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高级别浆液性卵巢癌(HGSOC)可能由低分化的干细胞样细胞(PDSLC)和分化型肿瘤细胞组成。常规治疗无法完全清除PDSLC,导致疾病进展和肿瘤复发。已知原代NK细胞能有效裂解PDSLC,但对高分化肿瘤的细胞毒性潜力较低或极低。我们在本综述中介绍并讨论了超级NK(sNK)细胞的特征。与原代NK细胞相比,sNK细胞对PDSLC和高分化肿瘤均表现出显著更强的直接杀伤能力。此外,sNK细胞分泌显著更高水平的细胞因子,尤其是那些已知能诱导肿瘤分化的细胞因子。此外,我们提出sNK细胞与化疗的联合方案可能是消除卵巢肿瘤异质性群体最有效的策略之一;sNK细胞既能裂解PDSLC和高分化肿瘤,又能诱导PDSLC分化,并可与化疗联合用于靶向高分化肿瘤和NK诱导分化的肿瘤。
High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they exhibit low or minimal cytotoxic potential against well-differentiated tumors.
We have introduced and discussed the characteristics of super-charged NK (sNK) cells in this review. sNK cells, in comparison to primary NK cells, exhibit a significantly higher capability for the direct killing of both PDSLCs and well-differentiated tumors.
In addition, sNK cells secrete significantly higher levels of cytokines, especially those known to induce the differentiation of tumors.
In addition, we propose that a combination of sNK and chemotherapy could be one of the most effective strategies to eliminate the heterogeneous population of ovarian tumors; sNK cells can lyse both PDSLCs and well-differentiated tumors, induce the differentiation of PDSLCs, and could be used in combination with chemotherapy to target both well-differentiated and NK-induced differentiated tumors.
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