The article was published on Cell in September 2020. Ahmed Sadik et al. (German Cancer Research Center, Heidelberg, Germany) revealed that IL4I1, a major AHR activating enzyme, enhances CLL progression through promoting AHR-driven cancer cell motility and suppressing adaptive immunity. Immune checkpoint blockade induces IL4I1.
Background & Aims & Conclusions
Tryptophan catabolic enzyme IDO1 and TDO2 is considered as the major mediators of AHR activation in humans. AHR target genes express in a context-specific manner across different tissues and ligands, which impedes systematic investigation of AHR activity and its upstream enzymes across human cancers.
The aim of this study is to identify new mediators of AHR activation in human tumors. A pan-tissue AHR signature is developed to enable the detection of AHR activity across different tissues and ligands.
IL4I1 is identified as a new mediator of AHR activation in 32 tumor types. It promotes cancer cell motility, suppresses adaptive immunity, enhances CLL progression, and is induced by immune checkpoint blockade. IL4I1 blockade could be a new option for cancer therapy.
