title: 1810011o10 Rik Inhibits the Antitumor Effect of Intratumoral CD8+T Cells through Suppression of Notch2 Pathway in a Murine Hepatocellular Carcinoma Model.
abstract: The mechanisms by which tumor-responsive CD8+T cells are regulated are important for understanding the tumor immunity and for developing new therapeutic strategies. In current study, we identified the expression of 1810011o10 Rik, which is the homolog of human thyroid cancer 1, in intratumoral activated CD8+T cells in a murine hepatocellular carcinoma (HCC) implantation model. To investigate the role of 1810011o10 Rik in the regulation of antitumor activity of CD8+T cells, normal CD8+T cells were transduced with 1810011o10 Rik-expressing lentiviruses. Although 1810011o10 Rik overexpression did not influence agonistic antibody-induced CD8+T cell activationin vitro, it inhibited the cytotoxic efficacy of CD8+T cells on HCC cellsin vivo. 1810011o10 Rik overexpression impeded CD8+T cell-mediated HCC cell apoptosis and favored tumor cell growthin vivo. Further investigation revealed that 1810011o10 Rik blocked the nuclear translocation of Notch2 intracellular domain, which is crucial for CD8+T cell activity. Furthermore, a briefin vitroexperiment suggested that both antigen-presenting cells and TGF-β might be necessary for the upregulation of Rik expression in activated CD8+T cells. In general, our study disclosed a novel mechanism underlying the negative regulation of antitumor CD8+T cells during HCC progression.
authors.affiliation: Department of Infectious Diseases, Renmin Hospital of Wuhan University , Wuhan , China.
authors.forename: Kai
authors.initials: K
authors.lastname: Dai
authors.affiliation: Department of Cardiology, The Central Hospital of Wuhan , Wuhan , China.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Pathology, Renmin Hospital of Wuhan University , Wuhan , China.
authors.forename: Ya-Bing
authors.initials: YB
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University , Wuhan , China.
authors.forename: Zu-Bing
authors.initials: ZB
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, Renmin Hospital of Wuhan University , Wuhan , China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, Renmin Hospital of Wuhan University , Wuhan , China.
authors.forename: Ying-An
authors.initials: YA
authors.lastname: Jiang
keywords: 1810011o10 Rik; CD8+ T cells; Notch2; hepatocellular carcinoma; immunity