title: Tumoral indoleamine 2, 3-dioxygenase 1 is regulated by monocytes and T lymphocytes collaboration in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Gene Engineering of The Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Qiyi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhan-Lian
authors.initials: ZL
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Chaoshuang
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Shicheng
authors.initials: S
authors.lastname: Su
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D018920:Coculture Techniques; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase
keywords: IDO1; T cells; monocytes; tumor cells