Lu Zhen, Xia Yun-Hong, Zhao Min, Zhang Bing, Dai Wen-Ting, Ding Lu, Hu Li-Xia, Bi Jin-Ling, Jiang Guo-Lin
Department of General Surgery, The Fourth Affiliated Hospital, Anhui Medical University, Hefei, China.
Department of Oncology, The Fourth Affiliated Hospital, Anhui Medical University, Hefei, China.
Oncotarget. 2017 Jul 5;8(33):54993-55002. doi: 10.18632/oncotarget.18990. eCollection 2017 Aug 15.
Tumor-specific hepatic stellate cells (tHSCs) positively participate in human hepatocellular carcinoma (HCC) tumorigenesis and progression. Our previous studies have shown that tHSCs co-culture with dendritic cells (DCs) induced DIgR2 (dendritic cell-derived immunoglobulin receptor 2) expression. The latter is a member of IgSF inhibitory receptor suppressing DCs-initiated antigen-specific T-cell responses. In the current study, we show that hepatic artery injection of DlgR2 siRNA significantly inhibited in-situ HCC xenograft growth in rat livers. Further, 5-FU-medied inhibition of in-situ HCC growth was dramatically sensitized with DlgR2 silence. DlgR2 siRNA injection indeed downregulated DlgR2 in ex-vivo cultured tumor-derived DCs (tDCs). More importantly, tDCs activity was boosted following DlgR2 siRNA. These cells presented with upregulated CD80, CD86 and MHC-II. Production of interleukin-12 and tumor necrosis factor-α was also increased in the DlgR2-silenced tDCs. We propose that DlgR2 knockdown likely boosts the activity of tumor-associated DCs, and inhibits growth of in-situ HCC xenografts.
肿瘤特异性肝星状细胞（tHSCs）积极参与人类肝细胞癌（HCC）的肿瘤发生和进展。我们之前的研究表明，tHSCs与树突状细胞（DCs）共培养可诱导DIgR2（树突状细胞衍生的免疫球蛋白受体2）表达。后者是IgSF抑制性受体的成员，可抑制DCs启动的抗原特异性T细胞反应。在本研究中，我们发现肝动脉注射DlgR2 siRNA可显著抑制大鼠肝脏原位HCC异种移植瘤的生长。此外，DlgR2沉默可显著增强5-氟尿嘧啶介导的原位HCC生长抑制作用。注射DlgR2 siRNA确实下调了体外培养的肿瘤来源DCs（tDCs）中的DlgR2。更重要的是，DlgR2 siRNA处理后tDCs的活性增强。这些细胞的CD80、CD86和MHC-II表达上调。DlgR2沉默的tDCs中白细胞介素-12和肿瘤坏死因子-α的产生也增加。我们认为，DlgR2基因敲低可能增强肿瘤相关DCs的活性，并抑制原位HCC异种移植瘤的生长。
