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已发表论文
低吲哚胺 2,3 - 双加氧酶 1 表达增强树突状细胞对肝细胞癌肿瘤细胞的反应
Authors Mo C , Hong M, Li Y, Huang D, Ji Q , Liu Y
Received 30 April 2025
Accepted for publication 16 September 2025
Published 20 September 2025 Volume 2025:12 Pages 2149—2167
DOI https://doi.org/10.2147/JHC.S530997
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Ahmed Kaseb
Chan Mo,1,2 Min Hong,1 Yunjia Li,1 Danping Huang,1 Qingyu Ji,3 Yuan Liu3
1Department of First Clinical Medical College, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China; 2Medical Laboratory of the Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, 518001, People’s Republic of China; 3College of Integrated Traditional Chinese and Western Medicine, Jining Medical University, Jining, Shandong, 272067, People’s Republic of China
Correspondence: Yuan Liu, College of Integrated Traditional Chinese and Western Medicine, Jining Medical University, No. 133, Hehua Road, Taibai Lake New District, Jining City, Shandong Province, 272067, People’s Republic of China, Email liuy1015@126.com
Aim: To investigate the effect of IDO1 expression levels in HCC on the distribution, infiltration, and anti-tumor immune response of mature DCs.
Methods: 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. 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 catalytic inhibitor epacadostat (EPA) to observe the effect of IDO1 on tumor growth and immune cells infiltration.
Results: Results of clinical tissue microarrays showed that compared with corresponding paracancerous tissues, the infiltration of mature DCs was significantly reduced in HCC cancer tissues with high expression of IDO1. Meanwhile, IDO1 was highly expressed in HCC cancer tissues with pathological grade I–II, high AFP levels (≥ 200μg/L), HBV-positivie, cirrhosis, distant metastasis and recurrence. Survival analysis showed that low IDO1 and high mature DCs cell infiltration were significantly associated with superior overall survival (OS). Correlation analysis further showed that IDO1 was negatively correlated with mature DCs. The in vitro cellular and in vivo animal experiments in this study showed that inhibition IDO1 helped to decrease the malignant biological behavior of HCC and enhance the response of immune cells to tumor cells.
Conclusion: IDO1 suppresses anti-tumor immunity in HCC, at least in part, by curtailing mDC infiltration. Targeting IDO1 may represent a promising immunotherapeutic strategy. However, its immunomodulatory effects must be validated in immunocompetent or humanized animal systems before clinical translation.
Keywords: hepatocellular carcinoma, indoleamine 2,3 dioxygenase 1, dendritic cells, T cells
1Department of First Clinical Medical College, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China; 2Medical Laboratory of the Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, 518001, People’s Republic of China; 3College of Integrated Traditional Chinese and Western Medicine, Jining Medical University, Jining, Shandong, 272067, People’s Republic of China
Correspondence: Yuan Liu, College of Integrated Traditional Chinese and Western Medicine, Jining Medical University, No. 133, Hehua Road, Taibai Lake New District, Jining City, Shandong Province, 272067, People’s Republic of China, Email liuy1015@126.com
Aim: To investigate the effect of IDO1 expression levels in HCC on the distribution, infiltration, and anti-tumor immune response of mature DCs.
Methods: 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. 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 catalytic inhibitor epacadostat (EPA) to observe the effect of IDO1 on tumor growth and immune cells infiltration.
Results: Results of clinical tissue microarrays showed that compared with corresponding paracancerous tissues, the infiltration of mature DCs was significantly reduced in HCC cancer tissues with high expression of IDO1. Meanwhile, IDO1 was highly expressed in HCC cancer tissues with pathological grade I–II, high AFP levels (≥ 200μg/L), HBV-positivie, cirrhosis, distant metastasis and recurrence. Survival analysis showed that low IDO1 and high mature DCs cell infiltration were significantly associated with superior overall survival (OS). Correlation analysis further showed that IDO1 was negatively correlated with mature DCs. The in vitro cellular and in vivo animal experiments in this study showed that inhibition IDO1 helped to decrease the malignant biological behavior of HCC and enhance the response of immune cells to tumor cells.
Conclusion: IDO1 suppresses anti-tumor immunity in HCC, at least in part, by curtailing mDC infiltration. Targeting IDO1 may represent a promising immunotherapeutic strategy. However, its immunomodulatory effects must be validated in immunocompetent or humanized animal systems before clinical translation.
Keywords: hepatocellular carcinoma, indoleamine 2,3 dioxygenase 1, dendritic cells, T cells