Open AccessTumoral indoleamine 2, 3-dioxygenase 1 is regulated by monocytes and T lymphocytes collaboration in hepatocellular carcinoma
Author(s) -
Qiyi Zhao,
Peipei Wang,
Zheping Huang,
Liang Peng,
Lin Chen,
Zhiliang Gao,
Shicheng Su
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.7438
Subject(s) - hepatocellular carcinoma , indoleamine 2,3 dioxygenase , epigenetics , medicine , peripheral blood mononuclear cell , christian ministry , cancer research , liver cancer , immunology , biology , in vitro , gene , theology , genetics , philosophy , tryptophan , amino acid
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.