Bidirectional regulatory role of IDO1 in hepatocellular carcinoma：Promotion of Occurrence but Suppression of Progression

Aims To investigate the clinical significance of indoleamine 2,3 dioxygenase 1 (IDO1) in the development of hepatocellular carcinoma (HCC). Methods In vitro , CCK-8, Key Fluor 488 Click-iT Edu ,wound healing, and Transwell assays were performed to explore the effect of IDO1 on the viability, proliferation, migration and invasion ability of HCC cell line SK-HEP1. In vivo , a subcutaneous xenograft tumor model of nude mice was established by subcutaneously inoculating SK-HEP1 and treated with IDO1 inhibitor epacadostat (EPA) to observe the effect of IDO1 on tumor growth and immune cells infiltration. Multiplex immunohistochemical staining was applied to detect the expression level of IDO1 and the infiltration of DCs in the HCC tissue microarray, including total 96 human HCC samples and 82 samples of matched adjacent normal tissues. Results The in vitro cellular and in vivo animal experiments in this study showed that inhibition of IDO1 expression helped to improve the malignant biological behavior of HCC and enhance the response of immune cells to tumor cells. Results of clinical tissue microarrays showed that compared with poorly differentiated HCC cancer tissues, the expression level of IDO1 in highly differentiated HCC cancer tissues was significantly increased.Meanwhile, compared with corresponding paracancer tissues, the infiltration of mature DCs were significantly reduced in highly differentiated HCC cancer tissues with high expression of IDO1, whereas in poorly differentiated HCC cancer tissues with low expression of IDO1, the infiltration of mature DCs were significantly increased. And IDO1 was highly expressed in HCC cancer tissues with pathological grade I-II, high AFP levels (≥ 200ug/L), HBV-positivie, cirrhosis, distant metastasis and recurrence. Conclusions IDO1 was abnormally expressed in HCC and was related to the degree of differentiation of HCC and the infiltration of immune cells and it might have bidirectional regulatory role in HCC: Promotion of Occurrence but Suppression of Progression.