Lentivirus‑mediated RNA interference targeting programmed death receptor ligand 1 increases the immunologic anti‑tumor effect of dendritic cell vaccination against pancreatic cancer in SCID‑hu mice

Wang,Jin; Sun,Mingbing; Zhu,Xinguo; Zhao,Hua; Mao,Deli; Zhang,Zhe; Zhao,Xin

doi:10.3892/ol.2019.10426

Lentivirus‑mediated RNA interference targeting programmed death receptor ligand 1 increases the immunologic anti‑tumor effect of dendritic cell vaccination against pancreatic cancer in SCID‑hu mice

Authors:
- Jin Wang
- Mingbing Sun
- Xinguo Zhu
- Hua Zhao
- Deli Mao
- Zhe Zhang
- Xin Zhao
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
Published online on: May 31, 2019 https://doi.org/10.3892/ol.2019.10426
Pages: 1539-1547
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Programmed death receptor ligand 1 (PD‑L1), which belongs to the B7 family, is overexpressed in a variety of human cancer types and serves a crucial role in immune escape by malignant cells. Programmed death receptor 1 (PD‑1) is a specific PD‑L1 receptor. PD‑1/PD‑L1 signaling inhibits the antitumor effects of dendritic cell (DC) immunization for tumor treatment. The aim of the present study was to determine whether inhibiting PD‑L1 may increase the immunologic anti‑tumor effect of dendritic cells against pancreatic cancer. In the present study, PD‑L1 levels in non‑cancerous and malignant tissue samples were compared, and the impact of PD‑L1 downregulation on human pancreatic cancer PaTu8988 cells was determined by lentivirus‑based RNA interference and DC immunotherapy. PD‑L1 expression in pancreatic specimens was assessed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemistry. PaTu8988 cells expressing reduced levels of PD‑L1 were generated by lentivirus‑based knockdown to assess the mechanism by which the inhibition of PD‑L1 signaling in DC immunization affects therapeutic outcomes in pancreatic cancer‑bearing SCID‑hu mice. PD‑L1 levels were markedly elevated in pancreatic adenocarcinoma samples compared with in non‑cancerous tissue. PD‑L1 silencing in pancreatic adenocarcinoma cells resulted in improved treatment outcomes of DC immunization in vitro and in vivo compared with traditional DC immunization. PD‑L1 silencing enhances the antitumor response of cytotoxic T cells by increasing interferon γ production in vitro. In vivo, this method prevented tumor growth and lung metastasis, and prolonged survival in the SCID‑hu model. In conclusion, the results of the present study suggested that suppressing PD‑L1 in malignant cells during DC immunization may be a useful tool for immunotherapy in pancreatic adenocarcinoma.

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