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:Infiltrating natural killer cells bind, lyse and increase chemotherapy efficacy in glioblastoma stem-like tumorospheres.
Infiltrating natural killer cells bind, lyse and increase chemotherapy efficacy in glioblastoma stem-like tumorospheres.
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胶质母细胞瘤仍然是最致命的原发性脑肿瘤。基于自然杀伤(NK)细胞的治疗是治疗胶质母细胞瘤的一种有前景的免疫治疗策略,因为这些细胞能够选择并裂解治疗耐药的胶质母细胞瘤干细胞样细胞(GSLCs)。使用超级NK细胞的免疫治疗具有作为抗肿瘤方法的潜力,因为我们发现其在2D和3D模型中杀伤患者来源的GSLCs的效率,可能逆转患者中也观察到的免疫抑制。除了其强大的细胞毒性外,NK细胞分泌IFN-,上调GSLC表面CD54和MHC I类分子的表达,并增加GSLCs对化疗药物的敏感性。此外,NK细胞在胶质母细胞瘤组织中血管周围区域的定位及其在肿瘤球中与GSLCs的密切接触表明其具有浸润胶质母细胞瘤肿瘤并靶向GSLCs的能力。由于GSLC在其分化阶段方面具有异质性和可塑性,应设计个性化免疫治疗策略以有效靶向胶质母细胞瘤。
Glioblastomas remain the most lethal primary brain tumors. Natural killer (NK) cell-based therapy is a promising immunotherapeutic strategy in the treatment of glioblastomas, since these cells can select and lyse therapy-resistant glioblastoma stem-like cells (GSLCs). Immunotherapy with super-charged NK cells has a potential as antitumor approach since we found their efficiency to kill patient-derived GSLCs in 2D and 3D models, potentially reversing the immunosuppression also seen in the patients.
In addition to their potent cytotoxicity, NK cells secrete IFN- , upregulate GSLC surface expression of CD54 and MHC class I and increase sensitivity of GSLCs to chemotherapeutic drugs.
Moreover, NK cell localization in peri-vascular regions in glioblastoma tissues and their close contact with GSLCs in tumorospheres suggests their ability to infiltrate glioblastoma tumors and target GSLCs. Due to GSLC heterogeneity and plasticity in regards to their stage of differentiation personalized immunotherapeutic strategies should be designed to effectively target glioblastomas.
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