Tumoral indoleamine 2, 3-dioxygenase 1 is regulated by monocytes and T lymphocytes collaboration in hepatocellular carcinoma
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Qiyi Zhao1,2, Pei-pei Wang1, Zhan-lian Huang1, Liang Peng1, Chaoshuang Lin1, Zhiliang Gao1,3, Shicheng Su4,5
1Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
2Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
3Guangdong Provincial Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
4Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
5Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Chaoshuang Lin, e-mail: [email protected]
Zhiliang Gao, e-mail: [email protected]
Shicheng Su, e-mail: [email protected]
Keywords: IDO1, tumor cells, monocytes, T cells
Received: January 18, 2016 Accepted: January 30, 2016 Published: February 17, 2016
Indoleamine 2, 3-Dioxygenase 1 (IDO1) in cancer cells plays a critical role in tumor immunosuppression. However, the precise mechanisms regulating tumoral IDO1 expression in tumor milieus remain unclear. Here, we reported that IDO1 expression in tumor cells of hepatocelluar carcinomas (HCC), displayed a discrete rather than uniform pattern. In vitro culture, human hepatoma cell lines did not constitutively express IDO1. Interestingly, co-culture with peripheral blood mononuclear cells (PBMC) significantly induced and maintained IDO1 expression in these tumor cells, predominantly through IFN-γ. Mechanistically, we showed that IDO1 expression in tumor cells was only induced when co-cultured with both T lymphocytes and monocytes. Moreover, the cooperation between T lymphocytes and monocytes played an indispensable role on the tumoral IDO1 expression in immunocompromised mice. Taken together, our data supported the notion that IDO1 expression in tumor cells might serve as a counter-regulatory mechanism regulated by immune system, and provided new insights into the collaborative action of different inflammatory cells in tumor immunosuppression.
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