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  1. 050 医学部, 大学院医学系研究科
  2. 0501 学術論文

Intratumoral expression levels of PD-L1, GZMA, and HLA-A along with oligoclonal T cell expansion associate with response to nivolumab in metastatic melanoma

http://hdl.handle.net/10091/00020983
cd826138-60ae-46a3-ac93-0d4d24c7ccaf
名前 / ファイル ライセンス アクション
Intratumoral Intratumoral expression levels of PD L1 GZMA and HLA A along with oligoclonal T cell expansion associate with response to nivolumab in metastatic.pdf
Item type 学術雑誌論文 / Journal Article(1)
公開日 2018-10-31
タイトル
言語 en
タイトル Intratumoral expression levels of PD-L1, GZMA, and HLA-A along with oligoclonal T cell expansion associate with response to nivolumab in metastatic melanoma
言語
言語 eng
キーワード
主題Scheme Other
主題 Metastatic melanoma
キーワード
主題Scheme Other
主題 nivolumab
キーワード
主題Scheme Other
主題 oligoclonal T cell expansion
キーワード
主題Scheme Other
主題 PD-1
キーワード
主題Scheme Other
主題 T-cell receptor sequencing
資源タイプ
資源 http://purl.org/coar/resource_type/c_6501
タイプ journal article
著者 Inoue, Hiroyuki

× Inoue, Hiroyuki

WEKO 106645

en Inoue, Hiroyuki

Search repository
Park, Jae-Hyun

× Park, Jae-Hyun

WEKO 106646

en Park, Jae-Hyun

Search repository
Kiyotani, Kazuma

× Kiyotani, Kazuma

WEKO 106647

en Kiyotani, Kazuma

Search repository
Zewde, Makda

× Zewde, Makda

WEKO 106648

en Zewde, Makda

Search repository
Miyashita, Azusa

× Miyashita, Azusa

WEKO 106649

en Miyashita, Azusa

Search repository
Jinnin, Masatoshi

× Jinnin, Masatoshi

WEKO 106650

en Jinnin, Masatoshi

Search repository
Kiniwa, Yukiko

× Kiniwa, Yukiko

WEKO 106651

en Kiniwa, Yukiko

Search repository
Okuyama, Ryuhei

× Okuyama, Ryuhei

WEKO 106652

en Okuyama, Ryuhei

Search repository
Tanaka, Ryota

× Tanaka, Ryota

WEKO 106653

en Tanaka, Ryota

Search repository
Fujisawa, Yasuhiro

× Fujisawa, Yasuhiro

WEKO 106654

en Fujisawa, Yasuhiro

Search repository
Kato, Hiroshi

× Kato, Hiroshi

WEKO 106655

en Kato, Hiroshi

Search repository
Morita, Akimichi

× Morita, Akimichi

WEKO 106656

en Morita, Akimichi

Search repository
Asai, Jun

× Asai, Jun

WEKO 106657

en Asai, Jun

Search repository
Katoh, Norito

× Katoh, Norito

WEKO 106658

en Katoh, Norito

Search repository
Yokota, Kenji

× Yokota, Kenji

WEKO 106659

en Yokota, Kenji

Search repository
Akiyama, Masashi

× Akiyama, Masashi

WEKO 106660

en Akiyama, Masashi

Search repository
Ihn, Hironobu

× Ihn, Hironobu

WEKO 106661

en Ihn, Hironobu

Search repository
Fukushima, Satoshi

× Fukushima, Satoshi

WEKO 106662

en Fukushima, Satoshi

Search repository
Nakamura, Yusuke

× Nakamura, Yusuke

WEKO 106663

en Nakamura, Yusuke

Search repository
信州大学研究者総覧へのリンク
氏名 Okuyama, Ryuhei
URL http://soar-rd.shinshu-u.ac.jp/profile/ja.ZpfNHFSF.html
出版者
出版者 TAYLOR & FRANCIS INC
引用
内容記述タイプ Other
内容記述 ONCOIMMUNOLOGY.5(9):e1204507(2016)
書誌情報 ONCOIMMUNOLOGY

巻 5, 号 9, p. e1204507, 発行日 2016-08-26
抄録
内容記述タイプ Abstract
内容記述 Immune checkpoint inhibitors blocking the interaction between programmed death-1 (PD-1) and PD-1 ligand-1 (PD-L1) are revolutionizing the cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immune-related genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment. We found that, in addition to the PD-L1 (p = 0.03), expression levels of PD-1 ligand-2 (PD-L2), granzyme A (GZMA) and human leukocyte antigen-A (HLA-A) in the pre-treatment tumors were significantly higher (p = 0.04, p = 0.01 and p = 0.006, respectively) in responders (n = 5) than in non-responders (n = 8). With nivolumab treatment, tumors in responders exhibited a substantial increase of CD8, GZMA and perforin 1 (PRF1) expression levels as well as increased ratio of TBX21/GATA3, suggesting dominancy of helper T cell type 1 (Th1) response to type 2 (Th2) response. T cell receptor β (TCR-β) repertoire analysis revealed oligoclonal expansion of tumor-infiltrating T lymphocytes (TILs) in the tumor tissues of the responders. Our findings suggest that melanoma harboring high PD-1 ligands (PD-L1 and PD-L2), GZMA and HLA-A expression may respond preferentially to nivolumab treatment, which can enhance Th1-skewed cellular immunity with oligoclonal expansion of TILs.
資源タイプ(コンテンツの種類)
内容記述タイプ Other
内容記述 Article
ISSN
収録物識別子タイプ PISSN
収録物識別子 2162-4011
PubMed
関連識別子
識別子タイプ PMID
関連識別子 https://www.ncbi.nlm.nih.gov/pubmed/27757299
関連名称
関連名称 27757299
DOI
関連識別子
識別子タイプ DOI
関連識別子 https://doi.org/10.1080/2162402X.2016.1204507
関連名称
関連名称 10.1080/2162402X.2016.1204507
権利
権利情報 © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC© Hiroyuki Inoue, Jae-Hyun Park, Kazuma Kiyotani, Makda Zewde, Azusa Miyashita, Masatoshi Jinnin, Yukiko Kiniwa, Ryuhei Okuyama, Ryota Tanaka, Yasuhiro Fujisawa, Hiroshi Kato, Akimichi Morita, Jun Asai, Norito Katoh, Kenji Yokota, Masashi Akiyama, Hironobu Ihn, Satoshi Fukushima, and Yusuke Nakamura. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
WoS
表示名 Web of Science
URL http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000385528200006
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