PI3K/AKT/mTOR通路
癌症研究
无容量
阿维鲁单抗
Notch信号通路
免疫疗法
免疫系统
雷氏菌
生物
免疫检查点
依维莫司
血管生成
mTORC1型
免疫学
信号转导
细胞生物学
遗传学
作者
Shufen Han,Yu Xu,Chen Dong,Feiya Yang,Mingshuai Wang,Qiaoxia Zhou,Guoqiang Wang,Leo Li,Yu Xu,Wenxian Wang,Shangli Cai,Nianzeng Xing
出处
期刊:iScience
[Elsevier]
日期:2024-01-01
卷期号:27 (1): 108290-108290
标识
DOI:10.1016/j.isci.2023.108290
摘要
The evolutionarily conserved Notch pathway, involved in cancer stem cell capacity and cancer immunity, may predict the benefit from immune checkpoint inhibitors (ICIs) in clear cell renal cell carcinoma (ccRCC). In the TCGA dataset, mRNA expression of Notch pathway genes identified three clusters with different prognoses and molecular characteristics. Based on the differentially expressed Notch pathway genes between clusters, we constructed the Notch-score, correlated with Notch activation, angiogenesis, PI3K-AKT-mTOR activity, and sensitivities to VEGFR/mTOR inhibitors. A high Notch-score was linked with more "resting"/"anti-inflammatory" rather than "activated"/"pro-inflammatory" tumor-infiltrating immune cells, inactivated immune pathways, and scarce any benefits from ICI-based therapies over VEGFR/mTOR inhibitors in the JAVELIN Renal 101 (avelumab plus axitinib vs. sunitinib) and the CheckMate-009/010/025 trials (nivolumab vs. everolimus). For the Notch-activated ccRCCs, ICIs provide limited advantages and might not be strongly recommended, by which the cost-effectiveness of treatments in ccRCCs may be potentially improved.
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