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Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer

BACKGROUND: The purpose of the present study was to explore novel biomarkers that can predict the clinical outcome of patients before treatment or during vaccination. These would be useful for the selection of appropriate patients who would be expected to exhibit better treatment outcomes from vacci...

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Autores principales: Shindo, Yoshitaro, Hazama, Shoichi, Suzuki, Nobuaki, Iguchi, Haruo, Uesugi, Kazuhiro, Tanaka, Hiroaki, Aruga, Atsushi, Hatori, Takashi, Ishizaki, Hidenobu, Umeda, Yuzo, Fujiwara, Toshiyoshi, Ikemoto, Tetsuya, Shimada, Mitsuo, Yoshimatsu, Kazuhiko, Takenouchi, Hiroko, Matsui, Hiroto, Kanekiyo, Shinsuke, Iida, Michihisa, Koki, Yasunobu, Arima, Hideki, Furukawa, Hiroyuki, Ueno, Tomio, Yoshino, Shigefumi, Fujita, Tomonobu, Kawakami, Yutaka, Nakamura, Yusuke, Oka, Masaaki, Nagano, Hiroaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329922/
https://www.ncbi.nlm.nih.gov/pubmed/28241889
http://dx.doi.org/10.1186/s13046-017-0509-1
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author Shindo, Yoshitaro
Hazama, Shoichi
Suzuki, Nobuaki
Iguchi, Haruo
Uesugi, Kazuhiro
Tanaka, Hiroaki
Aruga, Atsushi
Hatori, Takashi
Ishizaki, Hidenobu
Umeda, Yuzo
Fujiwara, Toshiyoshi
Ikemoto, Tetsuya
Shimada, Mitsuo
Yoshimatsu, Kazuhiko
Takenouchi, Hiroko
Matsui, Hiroto
Kanekiyo, Shinsuke
Iida, Michihisa
Koki, Yasunobu
Arima, Hideki
Furukawa, Hiroyuki
Ueno, Tomio
Yoshino, Shigefumi
Fujita, Tomonobu
Kawakami, Yutaka
Nakamura, Yusuke
Oka, Masaaki
Nagano, Hiroaki
author_facet Shindo, Yoshitaro
Hazama, Shoichi
Suzuki, Nobuaki
Iguchi, Haruo
Uesugi, Kazuhiro
Tanaka, Hiroaki
Aruga, Atsushi
Hatori, Takashi
Ishizaki, Hidenobu
Umeda, Yuzo
Fujiwara, Toshiyoshi
Ikemoto, Tetsuya
Shimada, Mitsuo
Yoshimatsu, Kazuhiko
Takenouchi, Hiroko
Matsui, Hiroto
Kanekiyo, Shinsuke
Iida, Michihisa
Koki, Yasunobu
Arima, Hideki
Furukawa, Hiroyuki
Ueno, Tomio
Yoshino, Shigefumi
Fujita, Tomonobu
Kawakami, Yutaka
Nakamura, Yusuke
Oka, Masaaki
Nagano, Hiroaki
author_sort Shindo, Yoshitaro
collection PubMed
description BACKGROUND: The purpose of the present study was to explore novel biomarkers that can predict the clinical outcome of patients before treatment or during vaccination. These would be useful for the selection of appropriate patients who would be expected to exhibit better treatment outcomes from vaccination, and for facilitating the development of cancer vaccine treatments. METHODS: From a single-arm, non-randomized, human leukocyte antigen (HLA)-A-status-blind phase II trial of a vaccine treatment using three HLA-A*2402-restricted peptides for advanced pancreatic cancer (PC), we obtained peripheral blood samples from 36 patients of an HLA-A*2402-matched group and 27 patients of an HLA-A*2402-unmatched group. RESULTS: Multivariate analysis (HR = 2.546; 95% CI = 1.138 to 5.765; p = 0.0231) and log-rank test (p = 0.0036) showed that a high expression level of programmed death-1 (PD-1) on CD4+ T cells was a negative predictive biomarker of overall survival in the HLA-A*2402-matched group . Moreover, a high expression level of PD-1 on CD4+ T cells was a negative predictor for the induction of cytotoxic T lymphocytes (p = 0.0007). After treatment, we found that the upregulation of PD-1 and T cell immunoglobulin mucin-3 (Tim-3) expression on CD4+ and CD8+ T cells was significantly associated with a poor clinical outcome in the HLA-A*2402-matched group (p = 0.0330, 0.0282, 0.0046, and 0.0068, respectively). In contrast, there was no significant difference for these factors in the HLA-A*2402-unmatched group. CONCLUSIONS: Our results indicate that the upregulation of PD-1 and Tim-3 expression on CD4+ and CD8+ T cells may restrict T cell responses in advanced PC patients; therefore, combination immunotherapy with blockade of PD-1 and Tim-3 to restore T cell responses may be a potential therapeutic approach for advanced PC patients. TRIAL REGISTRATION: Clinical-Trail-Registration: UMIN000008082. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-017-0509-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-53299222017-03-03 Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer Shindo, Yoshitaro Hazama, Shoichi Suzuki, Nobuaki Iguchi, Haruo Uesugi, Kazuhiro Tanaka, Hiroaki Aruga, Atsushi Hatori, Takashi Ishizaki, Hidenobu Umeda, Yuzo Fujiwara, Toshiyoshi Ikemoto, Tetsuya Shimada, Mitsuo Yoshimatsu, Kazuhiko Takenouchi, Hiroko Matsui, Hiroto Kanekiyo, Shinsuke Iida, Michihisa Koki, Yasunobu Arima, Hideki Furukawa, Hiroyuki Ueno, Tomio Yoshino, Shigefumi Fujita, Tomonobu Kawakami, Yutaka Nakamura, Yusuke Oka, Masaaki Nagano, Hiroaki J Exp Clin Cancer Res Research BACKGROUND: The purpose of the present study was to explore novel biomarkers that can predict the clinical outcome of patients before treatment or during vaccination. These would be useful for the selection of appropriate patients who would be expected to exhibit better treatment outcomes from vaccination, and for facilitating the development of cancer vaccine treatments. METHODS: From a single-arm, non-randomized, human leukocyte antigen (HLA)-A-status-blind phase II trial of a vaccine treatment using three HLA-A*2402-restricted peptides for advanced pancreatic cancer (PC), we obtained peripheral blood samples from 36 patients of an HLA-A*2402-matched group and 27 patients of an HLA-A*2402-unmatched group. RESULTS: Multivariate analysis (HR = 2.546; 95% CI = 1.138 to 5.765; p = 0.0231) and log-rank test (p = 0.0036) showed that a high expression level of programmed death-1 (PD-1) on CD4+ T cells was a negative predictive biomarker of overall survival in the HLA-A*2402-matched group . Moreover, a high expression level of PD-1 on CD4+ T cells was a negative predictor for the induction of cytotoxic T lymphocytes (p = 0.0007). After treatment, we found that the upregulation of PD-1 and T cell immunoglobulin mucin-3 (Tim-3) expression on CD4+ and CD8+ T cells was significantly associated with a poor clinical outcome in the HLA-A*2402-matched group (p = 0.0330, 0.0282, 0.0046, and 0.0068, respectively). In contrast, there was no significant difference for these factors in the HLA-A*2402-unmatched group. CONCLUSIONS: Our results indicate that the upregulation of PD-1 and Tim-3 expression on CD4+ and CD8+ T cells may restrict T cell responses in advanced PC patients; therefore, combination immunotherapy with blockade of PD-1 and Tim-3 to restore T cell responses may be a potential therapeutic approach for advanced PC patients. TRIAL REGISTRATION: Clinical-Trail-Registration: UMIN000008082. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-017-0509-1) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-28 /pmc/articles/PMC5329922/ /pubmed/28241889 http://dx.doi.org/10.1186/s13046-017-0509-1 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Shindo, Yoshitaro
Hazama, Shoichi
Suzuki, Nobuaki
Iguchi, Haruo
Uesugi, Kazuhiro
Tanaka, Hiroaki
Aruga, Atsushi
Hatori, Takashi
Ishizaki, Hidenobu
Umeda, Yuzo
Fujiwara, Toshiyoshi
Ikemoto, Tetsuya
Shimada, Mitsuo
Yoshimatsu, Kazuhiko
Takenouchi, Hiroko
Matsui, Hiroto
Kanekiyo, Shinsuke
Iida, Michihisa
Koki, Yasunobu
Arima, Hideki
Furukawa, Hiroyuki
Ueno, Tomio
Yoshino, Shigefumi
Fujita, Tomonobu
Kawakami, Yutaka
Nakamura, Yusuke
Oka, Masaaki
Nagano, Hiroaki
Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer
title Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer
title_full Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer
title_fullStr Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer
title_full_unstemmed Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer
title_short Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer
title_sort predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase ii study on advanced pancreatic cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329922/
https://www.ncbi.nlm.nih.gov/pubmed/28241889
http://dx.doi.org/10.1186/s13046-017-0509-1
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