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:Natural killer cells have a synergistic anti-tumor effect in combination with chemoradiotherapy against head and neck cancer.
Natural killer cells have a synergistic anti-tumor effect in combination with chemoradiotherapy against head and neck cancer.
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我们的研究结果表明,NK 细胞与 CRT 联合对 HNSCC 具有强效的抗肿瘤作用。
自然杀伤(NK)细胞的应用是癌症免疫治疗领域一种有前景的方法;然而,需要联合治疗来增强NK细胞免疫治疗的效果。在本研究中,我们评估了放疗和顺铂作为放化疗(CRT)方案在头颈部鳞状细胞癌(HNSCC)中增强NK细胞免疫治疗效果的潜力。
NK细胞使用我们最近建立的K562-OX40配体和膜结合白细胞介素(IL)-18及IL-21饲养细胞,在IL-2/IL-15存在下,从健康供者外周血中扩增。
结果显示,在扩增过程中NK细胞的纯度以及NKG2D和淋巴细胞功能相关抗原1等活化标志物的表达增加,这与HNSCC患者的NK细胞浸润和总生存期呈正相关。CRT诱导HNSCC上的NK细胞活化配体(ULBP2)和黏附分子(ICAM-1、-2和-3),从而增强NK细胞对HNSCC的细胞毒性。
The use of natural killer (NK) cells is a promising approach in the field of cancer immunotherapy; however, combination treatments are required to enhance the effects of NK cell immunotherapy. In this study, we assessed the potential of irradiation and cisplatin as a chemoradiotherapy (CRT) regimen to augment the effects of NK cell immunotherapy in head and neck squamous cell carcinoma (HNSCC).
NK cells were expanded using our recently established K562-OX40 ligand and membrane-bound interleukin (IL)-18 and IL-21 feeder cells in the presence of IL-2/IL-15 from peripheral blood of healthy donors.
The results showed an increase in the purity of NK cells and expression of activation markers such as NKG2D and lymphocyte function-associated antigen 1 during the expansion process, which is positively correlated to the NK cell infiltration and overall survival in patients with HNSCC. CRT induced NK cell activation ligand (ULBP2) and adhesion molecules (ICAM-1, -2 and -3) on HNSCC, leading to enhanced cytotoxicity of NK cells against HNSCC.
Our findings suggest that the NK cells have a potent anti-tumor effect in combination with CRT against HNSCC.
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