TDO2 and tryptophan metabolites promote kynurenine/AhR signals to facilitate glioma progression and immunosuppression.
Chuanhong Zhong, Lilei Peng, Bei Tao, Senlin Yin, Liang Lyu, Hao Ding, Xiaobo Yang, Tangming Peng, Haiping He, Peizhi Zhou
Abstract
, resulting in sustained glioma cell proliferation. Mechanistically, overexpression of TDO2 promoted the secretion of Kyn, which in turn stimulated the activation of the aryl hydrocarbon receptor (AhR)/AKT signaling pathway, resulting in heightened proliferative properties and tumorigenic potential in glioma cells. Meanwhile, Kyn produced by tumor cells further suppressed the proliferation of functional T cells, thereby resulting in immunosuppression and enhanced tumor growth in glioma. Our study showed that TDO2-induced increase in tryptophan metabolite Kyn played a pivotal role in glioma development via the AhR/AKT pro-survival signals and immunosuppressive effects, suggesting that the use of TDO2 inhibitors in combination with chemotherapy may be a novel strategy to effectively and synergistically eliminate glioma cells.