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Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer by providing new options in addition to existing therapies. However, peptide vaccination therapies still represent an attractive approach, because of the antigen specificity. We identified survivin 2B peptide (SVN‐2B), a...

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Autores principales: Kubo, Terufumi, Tsurita, Giichiro, Hirohashi, Yoshihiko, Yasui, Hiroshi, Ota, Yasunori, Watanabe, Kazue, Murai, Aiko, Matsuo, Kazuhiko, Asanuma, Hiroko, Shima, Hiroaki, Wada, Satoshi, Nakatsugawa, Munehide, Kanaseki, Takayuki, Tsukahara, Tomohide, Mizuguchi, Toru, Hirata, Koichi, Takemasa, Ichiro, Imai, Kohzoh, Sato, Noriyuki, Torigoe, Toshihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676134/
https://www.ncbi.nlm.nih.gov/pubmed/31206934
http://dx.doi.org/10.1111/cas.14099
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author Kubo, Terufumi
Tsurita, Giichiro
Hirohashi, Yoshihiko
Yasui, Hiroshi
Ota, Yasunori
Watanabe, Kazue
Murai, Aiko
Matsuo, Kazuhiko
Asanuma, Hiroko
Shima, Hiroaki
Wada, Satoshi
Nakatsugawa, Munehide
Kanaseki, Takayuki
Tsukahara, Tomohide
Mizuguchi, Toru
Hirata, Koichi
Takemasa, Ichiro
Imai, Kohzoh
Sato, Noriyuki
Torigoe, Toshihiko
author_facet Kubo, Terufumi
Tsurita, Giichiro
Hirohashi, Yoshihiko
Yasui, Hiroshi
Ota, Yasunori
Watanabe, Kazue
Murai, Aiko
Matsuo, Kazuhiko
Asanuma, Hiroko
Shima, Hiroaki
Wada, Satoshi
Nakatsugawa, Munehide
Kanaseki, Takayuki
Tsukahara, Tomohide
Mizuguchi, Toru
Hirata, Koichi
Takemasa, Ichiro
Imai, Kohzoh
Sato, Noriyuki
Torigoe, Toshihiko
author_sort Kubo, Terufumi
collection PubMed
description Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer by providing new options in addition to existing therapies. However, peptide vaccination therapies still represent an attractive approach, because of the antigen specificity. We identified survivin 2B peptide (SVN‐2B), a 9‐mer antigenic peptide encoded by survivin, and an SVN‐2B peptide vaccine‐based phase II randomized clinical trial targeting unresectable and refractory pancreatic carcinoma was undertaken. The SVN‐2B peptide vaccine did not have any statistically significant clinical benefits in that study. Therefore, we undertook an autopsy study to analyze the immune status of the pancreatic cancer lesions at the histological level. Autopsies were carried out in 13 patients who had died of pancreatic cancer, including 7 who had received SVN‐2B peptide vaccination and 6 who had not, as negative controls. The expression of immune‐related molecules was analyzed by immunohistochemical staining. Cytotoxic T lymphocytes were analyzed by tetramer staining and enzyme‐linked immunospot assay. Histological analysis revealed dense infiltration of CD8(+) T cells in some lesions in patients who had received the SVN‐2B peptide vaccine. A high rate of programmed cell death ligand 1 expression in cancer cells was observed in these cases, indicating that CTLs were induced by SVN‐2B peptide vaccination and had infiltrated the lesions. The lack of a significant antitumor effect was most likely attributable to the expression of immune checkpoint molecules. These findings suggest that the combination of a tumor‐specific peptide vaccine and an ICI might be a promising approach to the treatment of pancreatic carcinoma in the future.
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spelling pubmed-66761342019-08-06 Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series Kubo, Terufumi Tsurita, Giichiro Hirohashi, Yoshihiko Yasui, Hiroshi Ota, Yasunori Watanabe, Kazue Murai, Aiko Matsuo, Kazuhiko Asanuma, Hiroko Shima, Hiroaki Wada, Satoshi Nakatsugawa, Munehide Kanaseki, Takayuki Tsukahara, Tomohide Mizuguchi, Toru Hirata, Koichi Takemasa, Ichiro Imai, Kohzoh Sato, Noriyuki Torigoe, Toshihiko Cancer Sci Original Articles Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer by providing new options in addition to existing therapies. However, peptide vaccination therapies still represent an attractive approach, because of the antigen specificity. We identified survivin 2B peptide (SVN‐2B), a 9‐mer antigenic peptide encoded by survivin, and an SVN‐2B peptide vaccine‐based phase II randomized clinical trial targeting unresectable and refractory pancreatic carcinoma was undertaken. The SVN‐2B peptide vaccine did not have any statistically significant clinical benefits in that study. Therefore, we undertook an autopsy study to analyze the immune status of the pancreatic cancer lesions at the histological level. Autopsies were carried out in 13 patients who had died of pancreatic cancer, including 7 who had received SVN‐2B peptide vaccination and 6 who had not, as negative controls. The expression of immune‐related molecules was analyzed by immunohistochemical staining. Cytotoxic T lymphocytes were analyzed by tetramer staining and enzyme‐linked immunospot assay. Histological analysis revealed dense infiltration of CD8(+) T cells in some lesions in patients who had received the SVN‐2B peptide vaccine. A high rate of programmed cell death ligand 1 expression in cancer cells was observed in these cases, indicating that CTLs were induced by SVN‐2B peptide vaccination and had infiltrated the lesions. The lack of a significant antitumor effect was most likely attributable to the expression of immune checkpoint molecules. These findings suggest that the combination of a tumor‐specific peptide vaccine and an ICI might be a promising approach to the treatment of pancreatic carcinoma in the future. John Wiley and Sons Inc. 2019-07-11 2019-08 /pmc/articles/PMC6676134/ /pubmed/31206934 http://dx.doi.org/10.1111/cas.14099 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Kubo, Terufumi
Tsurita, Giichiro
Hirohashi, Yoshihiko
Yasui, Hiroshi
Ota, Yasunori
Watanabe, Kazue
Murai, Aiko
Matsuo, Kazuhiko
Asanuma, Hiroko
Shima, Hiroaki
Wada, Satoshi
Nakatsugawa, Munehide
Kanaseki, Takayuki
Tsukahara, Tomohide
Mizuguchi, Toru
Hirata, Koichi
Takemasa, Ichiro
Imai, Kohzoh
Sato, Noriyuki
Torigoe, Toshihiko
Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series
title Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series
title_full Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series
title_fullStr Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series
title_full_unstemmed Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series
title_short Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series
title_sort immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2b peptide: analysis of an autopsy series
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676134/
https://www.ncbi.nlm.nih.gov/pubmed/31206934
http://dx.doi.org/10.1111/cas.14099
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