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Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells

Recent evidence suggest that a β-glucan derived from mushroom Schizophyllan(SPG) complexed with a humanized TLR9 agonistic CpG DNA, K3 (K3-SPG) is a promising vaccine adjuvant that induces robust CD8 T cell responses to co-administered antigen. However, it has not been investigated whether K3-SPG al...

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Autores principales: Kitahata, Yuji, Kanuma, Tomohiro, Hayashi, Masayuki, Kobayashi, Nobuyoshi, Ozasa, Koji, Kusakabe, Takato, Temizoz, Burcu, Kuroda, Etsushi, Yamaue, Hiroki, Coban, Cevayir, Yamamoto, Takuya, Kobiyama, Kouji, Aoshi, Taiki, Ishii, Ken J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226476/
https://www.ncbi.nlm.nih.gov/pubmed/27384490
http://dx.doi.org/10.18632/oncotarget.10379
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author Kitahata, Yuji
Kanuma, Tomohiro
Hayashi, Masayuki
Kobayashi, Nobuyoshi
Ozasa, Koji
Kusakabe, Takato
Temizoz, Burcu
Kuroda, Etsushi
Yamaue, Hiroki
Coban, Cevayir
Yamamoto, Takuya
Kobiyama, Kouji
Aoshi, Taiki
Ishii, Ken J.
author_facet Kitahata, Yuji
Kanuma, Tomohiro
Hayashi, Masayuki
Kobayashi, Nobuyoshi
Ozasa, Koji
Kusakabe, Takato
Temizoz, Burcu
Kuroda, Etsushi
Yamaue, Hiroki
Coban, Cevayir
Yamamoto, Takuya
Kobiyama, Kouji
Aoshi, Taiki
Ishii, Ken J.
author_sort Kitahata, Yuji
collection PubMed
description Recent evidence suggest that a β-glucan derived from mushroom Schizophyllan(SPG) complexed with a humanized TLR9 agonistic CpG DNA, K3 (K3-SPG) is a promising vaccine adjuvant that induces robust CD8 T cell responses to co-administered antigen. However, it has not been investigated whether K3-SPG alone can act as an anti-cancer immunotherapeutic agent or not. Here, we demonstrate that intravenous injection of K3-SPG, but not CpG alone, is accumulated in the tumor microenvironment and triggered immunogenic cell death (ICD) of tumor cells by local induction of type-I interferon (IFN) as well as IL-12. Resultant innate immune activation as well as subsequent tumor-specific CD8 T cell responses were contributed the tumor growth suppression. This anti-tumor effect of K3-SPG monotherapy was also confirmed by using various tumor models including pancreatic cancer peritoneal dissemination model. Taken together, nano-particulate TLR9 agonist injected intravenously can scout out tumor microenvironment to provoke local innate immune activation and release dead tumor cells into circulation that may induce broader and protective tumor antigen-specific CD8 T cells.
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spelling pubmed-52264762017-01-18 Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells Kitahata, Yuji Kanuma, Tomohiro Hayashi, Masayuki Kobayashi, Nobuyoshi Ozasa, Koji Kusakabe, Takato Temizoz, Burcu Kuroda, Etsushi Yamaue, Hiroki Coban, Cevayir Yamamoto, Takuya Kobiyama, Kouji Aoshi, Taiki Ishii, Ken J. Oncotarget Priority Research Paper Recent evidence suggest that a β-glucan derived from mushroom Schizophyllan(SPG) complexed with a humanized TLR9 agonistic CpG DNA, K3 (K3-SPG) is a promising vaccine adjuvant that induces robust CD8 T cell responses to co-administered antigen. However, it has not been investigated whether K3-SPG alone can act as an anti-cancer immunotherapeutic agent or not. Here, we demonstrate that intravenous injection of K3-SPG, but not CpG alone, is accumulated in the tumor microenvironment and triggered immunogenic cell death (ICD) of tumor cells by local induction of type-I interferon (IFN) as well as IL-12. Resultant innate immune activation as well as subsequent tumor-specific CD8 T cell responses were contributed the tumor growth suppression. This anti-tumor effect of K3-SPG monotherapy was also confirmed by using various tumor models including pancreatic cancer peritoneal dissemination model. Taken together, nano-particulate TLR9 agonist injected intravenously can scout out tumor microenvironment to provoke local innate immune activation and release dead tumor cells into circulation that may induce broader and protective tumor antigen-specific CD8 T cells. Impact Journals LLC 2016-07-01 /pmc/articles/PMC5226476/ /pubmed/27384490 http://dx.doi.org/10.18632/oncotarget.10379 Text en Copyright: © 2016 Kitahata et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Priority Research Paper
Kitahata, Yuji
Kanuma, Tomohiro
Hayashi, Masayuki
Kobayashi, Nobuyoshi
Ozasa, Koji
Kusakabe, Takato
Temizoz, Burcu
Kuroda, Etsushi
Yamaue, Hiroki
Coban, Cevayir
Yamamoto, Takuya
Kobiyama, Kouji
Aoshi, Taiki
Ishii, Ken J.
Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells
title Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells
title_full Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells
title_fullStr Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells
title_full_unstemmed Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells
title_short Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells
title_sort circulating nano-particulate tlr9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells
topic Priority Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226476/
https://www.ncbi.nlm.nih.gov/pubmed/27384490
http://dx.doi.org/10.18632/oncotarget.10379
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