Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is a common and lethal malignancy in the world [1,2,3]
We propose that DlgR2 knockdown likely boosts the activity of tumor-associated dendritic cells (DCs), and inhibits growth of in-situ hepatocellular carcinoma (HCC) xenografts
The bone marrow-derived dendritic cells were derived from the rat femurs using the described method [12]. mDCs were co-cultured with quiescent HSCs (qHSCs) or Tumor-specific hepatic stellate cells (tHSCs)
Summary
Hepatocellular carcinoma (HCC) is a common and lethal malignancy in the world [1,2,3]. Tumor immunity has received considerable attentions in the basic research and clinical treatment of HCC [7,8,9]. Dendritic cells (DCs) are antigen-presenting cells (APC), which are vital in both initiation and regulation of immune responses [10, 11]. Recent studies have focused extensively on the potential function of DCs in tumor immunity [10, 11]. DCs activation is extremely important for proper anti-tumor response [10, 11]. DCs depletion or inhibition, on the other hand, will result in a pro-cancerous environment [10, 11]
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