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:Assessment of anti-CD69 antibody therapy alone or in combination with anti-PD-1 in murine GBM.
Assessment of anti-CD69 antibody therapy alone or in combination with anti-PD-1 in murine GBM.
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这是首个在临床前 GBM 模型中评估抗 CD69 治疗的研究。尽管在其他癌症中临床前数据令人鼓舞,但抗 CD69 单药治疗或与抗 PD-1 联合治疗均未改善该 GBM 模型中的生存期。
胶质母细胞瘤(GBM)是一种侵袭性癌症,治疗选择有限。靶向CD69(T细胞上的早期激活标志物)的免疫疗法在非中枢神经系统恶性肿瘤的临床前模型中已显示出前景。本研究在临床前GBM模型中探讨了单独抗CD69治疗或与抗PD-1联合治疗。
使用TCGA数据库分析GBM患者组织中的CD69表达。在不同方案下,于小鼠GBM模型中测试抗CD69的治疗疗效。通过流式细胞术评估肿瘤微环境(TME)中的免疫细胞群体。
在GBM患者中观察到CD69表达增加,与正常脑组织相比,并与更差的预后相关。抗CD69治疗降低了CD69+免疫细胞的百分比,但并未改善GBM荷瘤小鼠的生存期。抗CD69治疗后观察到NK细胞上PD-1表达增加。在体内,加入抗PD-1并未改善抗CD69治疗的效果。
Glioblastoma (GBM) is an aggressive cancer with limited treatment options. Immunotherapy targeting CD69, an early activation marker on T cells, has shown promise in preclinical models of non-CNS malignancies. This study investigates anti-CD69 therapy alone or in combination with anti-PD-1 in a preclinical GBM model. RESEARCH DESIGN AND METHODS: CD69 expression in GBM patient tissues was analyzed using the TCGA database. Therapeutic efficacy of anti-CD69 was tested in a murine GBM model with different regimens. Immune cell populations in the tumor microenvironment (TME) were assessed by flow cytometry.
Increased CD69 expression was observed in GBM patients compared to normal brain tissue and was associated with worse prognosis. Anti-CD69 treatment reduced percentages of CD69 + immune cells but did not improve survival in GBM-bearing mice. Increased PD-1 expression on NK cells was observed following anti-CD69 treatment. Anti-CD69 treatment was not improved by the addition of anti-PD-1 in vivo.
This is the first study evaluating anti-CD69 therapy in a preclinical GBM model. Despite promising preclinical data in other cancers, anti-CD69 monotherapy or combination therapy with anti-PD-1 did not improve survival in this GBM model.
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