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Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides

In immunotherapy by cancer antigen-derived peptide vaccine, vaccination of cytotoxic T lymphocyte (CTL) peptide alone is common, while it remains unclear whether the addition of helper peptide vaccine to the CTL peptide vaccine is of great advantage for the enhancement of tumor immunity. In the pres...

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Autores principales: Nakata, Jun, Nakajima, Hiroko, Hayashibara, Hiromu, Imafuku, Kanako, Morimoto, Soyoko, Fujiki, Fumihiro, Motooka, Daisuke, Okuzaki, Daisuke, Hasegawa, Kana, Hosen, Naoki, Tsuboi, Akihiro, Oka, Yoshihiro, Kumanogoh, Atsushi, Oji, Yusuke, Sugiyama, Haruo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267595/
https://www.ncbi.nlm.nih.gov/pubmed/30542516
http://dx.doi.org/10.18632/oncotarget.26338
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author Nakata, Jun
Nakajima, Hiroko
Hayashibara, Hiromu
Imafuku, Kanako
Morimoto, Soyoko
Fujiki, Fumihiro
Motooka, Daisuke
Okuzaki, Daisuke
Hasegawa, Kana
Hosen, Naoki
Tsuboi, Akihiro
Oka, Yoshihiro
Kumanogoh, Atsushi
Oji, Yusuke
Sugiyama, Haruo
author_facet Nakata, Jun
Nakajima, Hiroko
Hayashibara, Hiromu
Imafuku, Kanako
Morimoto, Soyoko
Fujiki, Fumihiro
Motooka, Daisuke
Okuzaki, Daisuke
Hasegawa, Kana
Hosen, Naoki
Tsuboi, Akihiro
Oka, Yoshihiro
Kumanogoh, Atsushi
Oji, Yusuke
Sugiyama, Haruo
author_sort Nakata, Jun
collection PubMed
description In immunotherapy by cancer antigen-derived peptide vaccine, vaccination of cytotoxic T lymphocyte (CTL) peptide alone is common, while it remains unclear whether the addition of helper peptide vaccine to the CTL peptide vaccine is of great advantage for the enhancement of tumor immunity. In the present study, combination vaccine of Wilms’ tumor gene 1(WT1) protein-derived CTL and helper peptides induced the strong infiltration of WT1-specific CD8(+) T cells into mouse tumor at frequencies of 8.8%, resulting in the formation of multiple microscopic necrotic lesions in the tumor, whereas the frequencies of WT1-specific CD8(+) T cell infiltration into the tumor in the vaccination of the CTL peptide alone were only 0.32%. The majority of the infiltrated WT1-specific CD8(+) T cells was effector phenotype T cells, but importantly, WT1-specific CD8(+)CD44(+)CD62L(+)CD103(+) resident memory T cells, which could differentiate into a lot of effector phenotype T cells, existed in the tumor of mice vaccinated with the both WT1 peptides. Furthermore, T-cell receptor repertoire analysis showed the oligoclonality of these tumor infiltrating WT1 tetramer(+) CD8(+) T cells, and 3 clones occupied about half of them. These results indicated that WT1-specific CD4(+) T cells played an essential role not only in the priming and activation of WT1-specific CD8(+) T cells, but also in trafficking and infiltration of the CD8(+) T cells into tumors. These results should provide us with the concept that in the clinical setting, combination vaccine of WT1-specific CTL and helper peptides would be more advantageous than the CTL peptide vaccine alone.
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spelling pubmed-62675952018-12-12 Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides Nakata, Jun Nakajima, Hiroko Hayashibara, Hiromu Imafuku, Kanako Morimoto, Soyoko Fujiki, Fumihiro Motooka, Daisuke Okuzaki, Daisuke Hasegawa, Kana Hosen, Naoki Tsuboi, Akihiro Oka, Yoshihiro Kumanogoh, Atsushi Oji, Yusuke Sugiyama, Haruo Oncotarget Research Paper In immunotherapy by cancer antigen-derived peptide vaccine, vaccination of cytotoxic T lymphocyte (CTL) peptide alone is common, while it remains unclear whether the addition of helper peptide vaccine to the CTL peptide vaccine is of great advantage for the enhancement of tumor immunity. In the present study, combination vaccine of Wilms’ tumor gene 1(WT1) protein-derived CTL and helper peptides induced the strong infiltration of WT1-specific CD8(+) T cells into mouse tumor at frequencies of 8.8%, resulting in the formation of multiple microscopic necrotic lesions in the tumor, whereas the frequencies of WT1-specific CD8(+) T cell infiltration into the tumor in the vaccination of the CTL peptide alone were only 0.32%. The majority of the infiltrated WT1-specific CD8(+) T cells was effector phenotype T cells, but importantly, WT1-specific CD8(+)CD44(+)CD62L(+)CD103(+) resident memory T cells, which could differentiate into a lot of effector phenotype T cells, existed in the tumor of mice vaccinated with the both WT1 peptides. Furthermore, T-cell receptor repertoire analysis showed the oligoclonality of these tumor infiltrating WT1 tetramer(+) CD8(+) T cells, and 3 clones occupied about half of them. These results indicated that WT1-specific CD4(+) T cells played an essential role not only in the priming and activation of WT1-specific CD8(+) T cells, but also in trafficking and infiltration of the CD8(+) T cells into tumors. These results should provide us with the concept that in the clinical setting, combination vaccine of WT1-specific CTL and helper peptides would be more advantageous than the CTL peptide vaccine alone. Impact Journals LLC 2018-11-13 /pmc/articles/PMC6267595/ /pubmed/30542516 http://dx.doi.org/10.18632/oncotarget.26338 Text en Copyright: © 2018 Nakata et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Nakata, Jun
Nakajima, Hiroko
Hayashibara, Hiromu
Imafuku, Kanako
Morimoto, Soyoko
Fujiki, Fumihiro
Motooka, Daisuke
Okuzaki, Daisuke
Hasegawa, Kana
Hosen, Naoki
Tsuboi, Akihiro
Oka, Yoshihiro
Kumanogoh, Atsushi
Oji, Yusuke
Sugiyama, Haruo
Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides
title Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides
title_full Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides
title_fullStr Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides
title_full_unstemmed Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides
title_short Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides
title_sort extremely strong infiltration of wt1-specific ctls into mouse tumor by the combination vaccine with wt1-specific ctl and helper peptides
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267595/
https://www.ncbi.nlm.nih.gov/pubmed/30542516
http://dx.doi.org/10.18632/oncotarget.26338
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