PMID- 28241889
OWN - NLM
STAT- MEDLINE
DCOM- 20180205
LR  - 20181113
IS  - 1756-9966 (Electronic)
IS  - 0392-9078 (Print)
IS  - 0392-9078 (Linking)
VI  - 36
IP  - 1
DP  - 2017 Feb 28
TI  - Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the 
      results of a phase II study on advanced pancreatic cancer.
PG  - 36
LID - 10.1186/s13046-017-0509-1 [doi]
LID - 36
AB  - 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 .
FAU - Shindo, Yoshitaro
AU  - Shindo Y
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 
      755-8505, Japan.
FAU - Hazama, Shoichi
AU  - Hazama S
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 
      755-8505, Japan.
AD  - Department of Translational Research and Developmental Therapeutics against 
      Cancer, Yamaguchi University School of Medicine, Ube, Japan.
FAU - Suzuki, Nobuaki
AU  - Suzuki N
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 
      755-8505, Japan.
FAU - Iguchi, Haruo
AU  - Iguchi H
AD  - Clinical Research Center, Shikoku Cancer Center, NHO., Matsuyama, Japan.
FAU - Uesugi, Kazuhiro
AU  - Uesugi K
AD  - Clinical Research Center, Shikoku Cancer Center, NHO., Matsuyama, Japan.
FAU - Tanaka, Hiroaki
AU  - Tanaka H
AD  - Department of Surgical Oncology, Osaka City University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Aruga, Atsushi
AU  - Aruga A
AD  - Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
FAU - Hatori, Takashi
AU  - Hatori T
AD  - Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
FAU - Ishizaki, Hidenobu
AU  - Ishizaki H
AD  - Department of Surgical Oncology and Regulation of Organ Function, Miyazaki 
      University School of Medicine, Miyazaki, Japan.
FAU - Umeda, Yuzo
AU  - Umeda Y
AD  - Department of Gastroenterological Surgery, Okayama University Graduate School of 
      Medicine, Okayama, Japan.
FAU - Fujiwara, Toshiyoshi
AU  - Fujiwara T
AD  - Department of Gastroenterological Surgery, Okayama University Graduate School of 
      Medicine, Okayama, Japan.
FAU - Ikemoto, Tetsuya
AU  - Ikemoto T
AD  - Department of Digestive and Transplant Surgery, Tokushima University Graduate 
      School of Medicine, Tokushima, Japan.
FAU - Shimada, Mitsuo
AU  - Shimada M
AD  - Department of Digestive and Transplant Surgery, Tokushima University Graduate 
      School of Medicine, Tokushima, Japan.
FAU - Yoshimatsu, Kazuhiko
AU  - Yoshimatsu K
AD  - Department of Surgery, Tokyo Women's Medical University Medical Center East, 
      Tokyo, Japan.
FAU - Takenouchi, Hiroko
AU  - Takenouchi H
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 
      755-8505, Japan.
FAU - Matsui, Hiroto
AU  - Matsui H
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 
      755-8505, Japan.
FAU - Kanekiyo, Shinsuke
AU  - Kanekiyo S
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 
      755-8505, Japan.
FAU - Iida, Michihisa
AU  - Iida M
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 
      755-8505, Japan.
FAU - Koki, Yasunobu
AU  - Koki Y
AD  - Department of Pharmacy, Yamaguchi University Hospital, Ube, Japan.
FAU - Arima, Hideki
AU  - Arima H
AD  - Department of Pharmacy, Yamaguchi University Hospital, Ube, Japan.
FAU - Furukawa, Hiroyuki
AU  - Furukawa H
AD  - Department of Pharmacy, Yamaguchi University Hospital, Ube, Japan.
FAU - Ueno, Tomio
AU  - Ueno T
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 
      755-8505, Japan.
FAU - Yoshino, Shigefumi
AU  - Yoshino S
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 
      755-8505, Japan.
FAU - Fujita, Tomonobu
AU  - Fujita T
AD  - Division of Cellular Signaling, Institute for Advanced Medical Research, Keio 
      University School of Medicine, Tokyo, Japan.
FAU - Kawakami, Yutaka
AU  - Kawakami Y
AD  - Division of Cellular Signaling, Institute for Advanced Medical Research, Keio 
      University School of Medicine, Tokyo, Japan.
FAU - Nakamura, Yusuke
AU  - Nakamura Y
AD  - Section of Hematology/Oncology, Department of Medicine, The University of 
      Chicago, Chicago, Illinois, USA.
FAU - Oka, Masaaki
AU  - Oka M
AD  - Yamaguchi University, Yamaguchi, Japan.
FAU - Nagano, Hiroaki
AU  - Nagano H
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 
      755-8505, Japan. hnagano@yamaguchi-u.ac.jp.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170228
PL  - England
TA  - J Exp Clin Cancer Res
JT  - Journal of experimental & clinical cancer research : CR
JID - 8308647
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Cancer Vaccines)
RN  - 0 (HAVCR2 protein, human)
RN  - 0 (HLA-A*24:02 antigen)
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (Hepatitis A Virus Cellular Receptor 2)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (Vaccines, Subunit)
SB  - IM
MH  - Aged
MH  - Biomarkers, Tumor/*blood
MH  - CD4-Positive T-Lymphocytes/metabolism
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Cancer Vaccines/*administration & dosage/therapeutic use
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - HLA-A24 Antigen/chemistry
MH  - Hepatitis A Virus Cellular Receptor 2/blood
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pancreatic Neoplasms/*drug therapy/immunology/pathology
MH  - Programmed Cell Death 1 Receptor/blood
MH  - Treatment Outcome
MH  - Up-Regulation
MH  - Vaccines, Subunit/*administration & dosage/therapeutic use
PMC - PMC5329922
OTO - NOTNLM
OT  - PD-1
OT  - Pancreatic cancer
OT  - Peptide vaccine
OT  - Predictive biomarker
OT  - Tim-3
EDAT- 2017/03/01 06:00
MHDA- 2018/02/06 06:00
PMCR- 2017/02/28
CRDT- 2017/03/01 06:00
PHST- 2016/12/16 00:00 [received]
PHST- 2017/02/22 00:00 [accepted]
PHST- 2017/03/01 06:00 [entrez]
PHST- 2017/03/01 06:00 [pubmed]
PHST- 2018/02/06 06:00 [medline]
PHST- 2017/02/28 00:00 [pmc-release]
AID - 10.1186/s13046-017-0509-1 [pii]
AID - 509 [pii]
AID - 10.1186/s13046-017-0509-1 [doi]
PST - epublish
SO  - J Exp Clin Cancer Res. 2017 Feb 28;36(1):36. doi: 10.1186/s13046-017-0509-1.