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:Supercharged NK Cell-Based Immuotherapy in Humanized Bone Marrow Liver and Thymus (Hu-BLT) Mice Model of Oral, Pancreatic, Glioblastoma, Hepatic, Melanoma and Ovarian Cancers.
Supercharged NK Cell-Based Immuotherapy in Humanized Bone Marrow Liver and Thymus (Hu-BLT) Mice Model of Oral, Pancreatic, Glioblastoma, Hepatic, Melanoma and Ovarian Cancers.
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本文综述多项体内外研究,探讨增强型自然杀伤(sNK)细胞疗法清除或治疗癌症的效果。我们利用人源化骨髓-肝脏-胸腺(hu-BLT)小鼠开展研究,覆盖口腔癌、胰腺癌、胶质母细胞瘤、黑色素瘤、肝癌和卵巢癌等6种肿瘤模型。体外研究显示,原代NK细胞优先靶向癌症干细胞样细胞(CSC)或低分化肿瘤;相比之下,与活化的原代NK细胞相比,sNK细胞对CSC/低分化肿瘤以及高分化肿瘤的靶向能力均显著更强。人源化BLT小鼠体内研究显示,单用sNK细胞或与其他抗癌疗法联合均可阻止肿瘤生长和转移。
此外,sNK细胞可增强骨髓、脾脏、牙龈、胰腺和外周血免疫细胞的IFN-γ分泌及细胞毒功能。体内外研究还显示,sNK细胞可促进CD8+ T细胞扩增并增强其功能。
总体而言,我们的研究表明,单用sNK细胞或联合其他抗癌疗法不仅能有效清除侵袭性肿瘤,还能增强CD8+ T细胞扩增和功能,使其进一步靶向癌细胞,为根除癌症并实现治愈提供一种可行策略。
In this paper, we review a number of in vitro and in vivo studies regarding the efficacy of supercharged NK (sNK) cell therapy in elimination or treatment of cancer.
We have performed studies using six different types of cancer models of oral, pancreatic, glioblastoma, melanoma, hepatic and ovarian cancers using hu-BLT mice.
Our in vitro studies demonstrated that primary NK cells preferentially target cancer stem-like cells (CSCs)/poorly differentiated tumors whereas sNK cells target both CSCs/poorly-differentiated and well-differentiated tumors significantly higher than primary activated NK cells.
Our in vivo studies in humanized-BLT mice showed that sNK cells alone or in combination with other cancer therapeutics prevented tumor growth and metastasis.
In addition, sNK cells were able to increase IFN- secretion and cytotoxic function by the immune cells in bone marrow, spleen, gingiva, pancreas and peripheral blood.
Furthermore, sNK cells were able to increase the expansion and function of CD8+ T cells both in in vitro and in vivo studies.
Overall, our studies demonstrated that sNK cells alone or in combination with other cancer therapeutics were not only effective against eliminating aggressive cancers, but were also able to increase the expansion and function of CD8+ T cells to further target cancer cells, providing a successful approach to eradicate and cure cancer.
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