Synergistic anti‐pancreatic cancer immunological effects by treatment with reduced expression in immortalized cells/dickkopf‐3 protein and peripheral blood mononuclear cells

Uchida, Daisuke; Shiraha, Hidenori; Kato, Hironari; Sawahara, Hiroaki; Nagahara, Teruya; Iwamuro, Masaya; Kataoka, Junro; Horiguchi, Shigeru; Watanabe, Masami; Takaki, Akinobu; Nouso, Kazuhiro; Nasu, Yasutomo; Kumon, Hiromi; Yamamoto, Kazuhide

doi:10.1111/jgh.13259

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…The limitation of this study is that our experimental model could not fully testify the immunological effect of Ad‐SGE‐REIC against HCC. In previous reports, REIC/Dkk‐3 was found to induce the activation of anti‐cancer immunity . When REIC/Dkk‐3 is overexpressed via Ad‐REIC in normal cells, ER stress‐induced signaling of the p38 and interferon regulatory factor 1 pathways is activated.…”

Section: Discussionmentioning

confidence: 87%

“…In previous reports, REIC/Dkk-3 was found to induce the activation of anti-cancer immunity. 8,16,18,39,40 When REIC/Dkk-3 is overexpressed via Ad-REIC in normal cells, ER stress-induced signaling of the p38 and interferon regulatory factor 1 pathways is activated. ER stress mediates enhanced IL-7 expression, resulting in the activation of the systemic immune response involving natural killer cells.…”

Section: Discussionmentioning

confidence: 99%

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Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf‐3 expressing adenoviral vector for hepatocellular carcinoma

Sawahara

Shiraha

Uchida

et al. 2017

J of Gastro and Hepatol

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf‐3 expressing adenoviral vector for hepatocellular carcinoma

Sawahara

Shiraha

Uchida

et al. 2017

J of Gastro and Hepatol

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“…Exogenous DKK3 inhibited T cell activity, and when DKK3 function was blocked, CD8 T cell proliferation and interleukin-2 (IL-2) production were restored (28,29). However, the precise role of DKK3 in the tumor immune response is far from clear, because conflicting reports also describe an immunostimulatory effect of DKK3 in lung and pancreatic cancer models (30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

Suppression of stromal-derived Dickkopf-3 (DKK3) inhibits tumor progression and prolongs survival in pancreatic ductal adenocarcinoma

et al. 2018

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Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and it is unclear whether its stromal infiltrate contributes to its aggressiveness. Here, we demonstrate that Dickkopf-3 (DKK3) is produced by pancreatic stellate cells and is present in most human PDAC. DKK3 stimulates PDAC growth, metastasis, and resistance to chemotherapy with both paracrine and autocrine mechanisms through NF-κB activation. Genetic ablation of DKK3 in an autochthonous model of PDAC inhibited tumor growth, induced a peritumoral infiltration of CD8+ T cells, and more than doubled survival. Treatment with a DKK3-blocking monoclonal antibody inhibited PDAC progression and chemoresistance and prolonged survival. The combination of DKK3 inhibition with immune checkpoint inhibition was more effective in reducing tumor growth than either treatment alone and resulted in a durable improvement in survival, suggesting that DKK3 neutralization may be effective as a single targeted agent or in combination with chemotherapy or immunotherapy for PDAC.

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“…These findings suggest that intracellular overexpression of REIC/Dkk-3 plays a distinct role in apoptosis induction and anti-oncogenic activity. However, there are only a few reports on the immunological reaction to secretory or exogenous REIC/Dkk-3 protein 11 12 13 .…”

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confidence: 99%

A super gene expression system enhances the anti-glioma effects of adenovirus-mediated REIC/Dkk-3 gene therapy

Oka

Kurozumi

Shimazu

et al. 2016

Sci Rep

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Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and therapeutic gene in many human cancers. Recently, an adenovirus REIC vector with the super gene expression system (Ad-SGE-REIC) was developed to increase REIC/Dkk-3 expression and enhance therapeutic effects compared with the conventional adenoviral vector (Ad-CAG-REIC). In this study, we investigated the in vitro and in vivo effects of Ad-SGE-REIC on malignant glioma. In U87ΔEGFR and GL261 glioma cells, western blotting confirmed that robust upregulation of REIC/Dkk-3 expression occurred in Ad-SGE-REIC-transduced cells, most notably after transduction at a multiplicity of infection of 10. Cytotoxicity assays showed that Ad-SGE-REIC resulted in a time-dependent and significant reduction in the number of malignant glioma cells attaching to the bottom of culture wells. Xenograft and syngeneic mouse intracranial glioma models treated with Ad-SGE-REIC had significantly longer survival than those treated with the control vector Ad-LacZ or with Ad-CAG-REIC. This study demonstrated the anti-glioma effect of Ad-SGE-REIC, which may represent a promising strategy for the treatment of malignant glioma.

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Synergistic anti‐pancreatic cancer immunological effects by treatment with reduced expression in immortalized cells/dickkopf‐3 protein and peripheral blood mononuclear cells

Cited by 6 publications

References 32 publications

Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf‐3 expressing adenoviral vector for hepatocellular carcinoma

Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf‐3 expressing adenoviral vector for hepatocellular carcinoma

Suppression of stromal-derived Dickkopf-3 (DKK3) inhibits tumor progression and prolongs survival in pancreatic ductal adenocarcinoma

A super gene expression system enhances the anti-glioma effects of adenovirus-mediated REIC/Dkk-3 gene therapy

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