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.
肿瘤细胞治疗研究
英文原题:Evaluating a combination treatment of NK cells and reovirus against bladder cancer cells using an in vitro assay to simulate intravesical therapy.
Evaluating a combination treatment of NK cells and reovirus against bladder cancer cells using an in vitro assay to simulate intravesical therapy.
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膀胱内给予呼肠孤病毒或自然杀伤(NK)细胞,均可有效治疗膀胱癌细胞(BCC);但相应单药治疗的细胞毒作用通常有限。此前尚未研究通过膀胱内途径局部联合高剂量呼肠孤病毒和NK细胞治疗的潜力。
本研究评估呼肠孤病毒和扩增NK(eNK)细胞作为膀胱癌潜在治疗策略的效果。研究在模拟膀胱内治疗的体外模型中,考察呼肠孤病毒3型Dearing株(RC402和RP116)单药治疗,以及与IL-18/IL-21预处理eNK细胞联合治疗对BCC细胞系(5637、HT-1376和253J-BV)的抗肿瘤作用。单用RP116或IL-18/IL-21预处理eNK细胞,对1级癌细胞(5637)均有有效细胞毒作用,但对HT-1376(2级癌)和来源于转移灶的253J-BV细胞无效。
值得注意的是,RP116联合IL-18/IL-21预处理eNK细胞对HT-1376和253J-BV细胞均显示有效细胞毒作用。研究结果凸显了呼肠孤病毒联合NK细胞治疗作为膀胱癌潜在策略的前景。
Intravesical treatment using either reovirus or natural killer (NK) cells serves as an efficient strategy for the treatment of bladder cancer cells (BCCs); however, corresponding monotherapies have often shown modest cytotoxicity. The potential of a locoregional combination using high-dose reovirus and NK cell therapy in an intravesical approach has not yet been studied. In this study, we evaluated the effectiveness of reoviruses and expanded NK cells (eNK) as potential strategies for the treatment of bladder cancer.
The anti-tumor effects of mono-treatment with reovirus type 3 Dearing strain (RC402 and RP116) and in combination with interleukin (IL)-18/-21-pretreated eNK cells were investigated on BCC lines (5637, HT-1376, and 253J-BV) using intravesical therapy to simulate in vitro model. RP116 and IL-18/-21-pretreated eNK cells exhibited effective cytotoxicity against grade 1 carcinoma (5637 cells) when used alone, but not against HT-1376 (grade 2 carcinoma) and 253J-BV cells (derived from a metastatic site).
Notably, combining RP116 with IL-18/-21-pretreated eNK cells displayed effective cytotoxicity against both HT-1376 and 253J-BV cells.
Our findings underscore the potential of a combination therapy using reoviruses and NK cells as a promising strategy for treating bladder cancer.
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