Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Jin, Sun, Mingbing, Zhu, Xinguo, Zhao, Hua, Mao, Deli, Zhang, Zhe, Zhao, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607057/
https://www.ncbi.nlm.nih.gov/pubmed/31423221
http://dx.doi.org/10.3892/ol.2019.10426
_version_ 1783432018207440896
author Wang, Jin
Sun, Mingbing
Zhu, Xinguo
Zhao, Hua
Mao, Deli
Zhang, Zhe
Zhao, Xin
author_facet Wang, Jin
Sun, Mingbing
Zhu, Xinguo
Zhao, Hua
Mao, Deli
Zhang, Zhe
Zhao, Xin
author_sort Wang, Jin
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6607057
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-66070572019-08-18 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 Oncol Lett Articles 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. D.A. Spandidos 2019-08 2019-05-31 /pmc/articles/PMC6607057/ /pubmed/31423221 http://dx.doi.org/10.3892/ol.2019.10426 Text en Copyright: © Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Wang, Jin
Sun, Mingbing
Zhu, Xinguo
Zhao, Hua
Mao, Deli
Zhang, Zhe
Zhao, Xin
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607057/
https://www.ncbi.nlm.nih.gov/pubmed/31423221
http://dx.doi.org/10.3892/ol.2019.10426
work_keys_str_mv AT wangjin lentivirusmediatedrnainterferencetargetingprogrammeddeathreceptorligand1increasestheimmunologicantitumoreffectofdendriticcellvaccinationagainstpancreaticcancerinscidhumice
AT sunmingbing lentivirusmediatedrnainterferencetargetingprogrammeddeathreceptorligand1increasestheimmunologicantitumoreffectofdendriticcellvaccinationagainstpancreaticcancerinscidhumice
AT zhuxinguo lentivirusmediatedrnainterferencetargetingprogrammeddeathreceptorligand1increasestheimmunologicantitumoreffectofdendriticcellvaccinationagainstpancreaticcancerinscidhumice
AT zhaohua lentivirusmediatedrnainterferencetargetingprogrammeddeathreceptorligand1increasestheimmunologicantitumoreffectofdendriticcellvaccinationagainstpancreaticcancerinscidhumice
AT maodeli lentivirusmediatedrnainterferencetargetingprogrammeddeathreceptorligand1increasestheimmunologicantitumoreffectofdendriticcellvaccinationagainstpancreaticcancerinscidhumice
AT zhangzhe lentivirusmediatedrnainterferencetargetingprogrammeddeathreceptorligand1increasestheimmunologicantitumoreffectofdendriticcellvaccinationagainstpancreaticcancerinscidhumice
AT zhaoxin lentivirusmediatedrnainterferencetargetingprogrammeddeathreceptorligand1increasestheimmunologicantitumoreffectofdendriticcellvaccinationagainstpancreaticcancerinscidhumice