癌症研究
肿瘤微环境
转移
癌症
免疫疗法
肺癌
细胞因子
癌症干细胞
PI3K/AKT/mTOR通路
癌细胞
免疫学
肿瘤进展
医学
生物
信号转导
病理
内科学
细胞生物学
肿瘤细胞
作者
Mengjia Song,Ping Yü,Kai Zhang,Yang Li,Feng Li,Chaoqi Zhang,Shaoyan Cheng,Dongli Yue,Nomathamsanqa Resegofetse Maimela,Jiao Qu,Shasha Li,Ting Sun,Zihai Li,Jianchuan Xia,Bin Zhang,Liping Wang,Yi Zhang
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2019-07-15
卷期号:79 (14): 3737-3748
被引量:78
标识
DOI:10.1158/0008-5472.can-19-0596
摘要
IFNγ is conventionally recognized as an inflammatory cytokine that plays a central role in antitumor immunity. Although it has been used clinically to treat a variety of malignancies, low levels of IFNγ in the tumor microenvironment (TME) increase the risk of tumor metastasis during immunotherapy. Accumulating evidence suggests that IFNγ can induce cancer progression, yet the mechanisms underlying the controversial role of IFNγ in tumor development remain unclear. Here, we reveal a dose-dependent effect of IFNγ in inducing tumor stemness to accelerate cancer progression in patients with a variety of cancer types. Low levels of IFNγ endowed cancer stem-like properties via the intercellular adhesion molecule-1 (ICAM1)-PI3K-Akt-Notch1 axis, whereas high levels of IFNγ activated the JAK1-STAT1-caspase pathway to induce apoptosis in non-small cell lung cancer (NSCLC). Inhibition of ICAM1 abrogated the stem-like properties of NSCLC cells induced by the low dose of IFNγ both in vitro and in vivo. This study unveils the role of low levels of IFNγ in conferring tumor stemness and elucidates the distinct signaling pathways activated by IFNγ in a dose-dependent manner, thus providing new insights into cancer treatment, particularly for patients with low expression of IFNγ in the TME. SIGNIFICANCE: These findings reveal the dose-dependent effect of IFNγ in inducing tumor stemness and elucidate the distinct molecular mechanisms activated by IFNγ in a dose-dependent manner.
科研通智能强力驱动
Strongly Powered by AbleSci AI