IL4I1-driven AHR signature: a new avenue for cancer therapy
Zuli Wang, Tiansheng Li, Chao Mao, Wenliang Liu, Yongguang Tao
Abstract
Aryl hydrocarbon receptor (AHR) was considered to be an important pan-tumor therapeutic target, but small molecule inhibitors targeting AHR target gene IDO1 have failed in clinical trials. The recent paper published in Cell by Opitz et al. explained the failure of previous clinical trials and identified new therapeutic targets 1 (Fig. 1 ). Fig. 1 Newly identified IL4I1 which is induced by immune checkpoint blockade (ICB) mediates AHR signature genes through I3P-KynA/I3A metabolic pathway parallel to IDO1 and/or TDO2-driven AHR signaling. On one hand, IL4I1 can promote cancer cell motility and metastasis, on the other hand, it also inhibits T-cell proliferation and recruits suppressive immune cells Full size image