Low-dose IFNg induces tumor cell stemness in tumor microenvironment of non–small cell lung cancer

Mengjia Song, Yu Ping, Kai Zhang, Li Yang, Feng Li, Chaoqi Zhang, Shaoyan Cheng, Dongli Yue, Nomathamsanqa Resegofetse Maimela, Jiao Qu, Shasha Liu, Ting Sun, Zihai Li, Jianchuan Xia, Bin Zhang, Liping Wang, Yi Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


IFNg is conventionally recognized as an inflammatory cyto-STAT1–caspase pathway to induce apoptosis in non–small cell kine that plays a central role in antitumor immunity. Although it lung cancer (NSCLC). Inhibition of ICAM1 abrogated the stem-has been used clinically to treat a variety of malignancies, low like properties of NSCLC cells induced by the low dose of IFNg levels of IFNg in the tumor microenvironment (TME) increase both in vitro and in vivo. This study unveils the role of low levels the risk of tumor metastasis during immunotherapy. Accumu-of IFNg in conferring tumor stemness and elucidates the distinct lating evidence suggests that IFNg can induce cancer progres-signaling pathways activated by IFNg in a dose-dependent sion, yet the mechanisms underlying the controversial role of manner, thus providing new insights into cancer treatment, IFNg in tumor development remain unclear. Here, we reveal a particularly for patients with low expression of IFNg in the TME. dose-dependent effect of IFNg in inducing tumor stemness to accelerate cancer progression in patients with a variety of cancer Significance: These findings reveal the dose-dependent types. Low levels of IFNg endowed cancer stem-like properties effect of IFNg in inducing tumor stemness and elucidate the via the intercellular adhesion molecule-1 (ICAM1)–PI3K–Akt–distinct molecular mechanisms activated by IFNg in a dose-Notch1 axis, whereas high levels of IFNg activated the JAK1–dependent manner.

Original languageEnglish (US)
Pages (from-to)3737-3748
Number of pages12
JournalCancer Research
Issue number14
StatePublished - 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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