アクセス数 : ?
ダウンロード数 : ?
ID 115981
タイトル別表記
PD-1/PD-L1経路の阻害は線維細胞の抗原提示能を増強する
BLOCKADE OF PD-1/PD-L1 ENHANCES APC FUNCTION OF FIBROCYTES
著者
アフローズ, タニア 徳島大学大学院医科学教育部(医学専攻)
Nguyen, Na Thi Tokushima University
Sugimoto, Masamichi Chugai Pharmaceutical
Kondoh, Osamu Chugai Pharmaceutical
キーワード
Fibrocytes
PD-1/PD-L1 Blockade
CD8+ T-cells
Antigen-presentation
Cancer immunotherapy
資料タイプ
学位論文
抄録
Fibrocytes, a distinct population of collagen-producing, monocyte-derived cells, are involved in wound healing as well as fibrotic diseases. Recently, fibrocytes have been revealed to play a role in the tumor microenvironment, particularly under antiangiogenic therapy. In addition, combination cancer immunotherapy with immune checkpoint inhibitor and antiangiogenic agents have been developed for various cancers in the clinical setting, although the immunological background is not clear. In the current study, we aimed to determine the function of fibrocytes in tumor immunity induced by immune checkpoint inhibitor therapy. Human and murine fibrocytes were generated from PBMCs and lungs, respectively. The expression of costimulatory and inhibitory molecules on fibrocytes was examined by flow cytometry. The stimulation of CD8+ T cells by fibrocytes was examined in MLRs with a 3H-thymidine incorporation assay. Fibrocytes expressed CD80low and CD86high as a costimulatory molecule, and expressed PD-L1high, but not PD-L2, as a coinhibitory molecule.Without any stimulation, fibrocytes strongly enhanced the proliferation of CD8+ T cells in mice and humans. Treatment with anti-CD86 and -CD54 Abs inhibited the growth of CD8+ T cells induced by fibrocytes. Anti–PD-L1 Ab further enhanced the proliferation of CD8+ T cells, even in the OVA-specific MLR with OT-1Rag-/- mice. Importantly, fibrocytes derived from PBMCs of patients with lung adenocarcinoma or murine MC38 tumors augmented the proliferation of CD8+ T cells with PD-L1 blockade. These results suggest that fibrocytes infiltrating tumor sites may play a role in the antitumor immunity mediated by CD8+ T cells when the activity is further enhanced by PD-L1/PD-1 blockade.
掲載誌名
The Journal of Immunology
ISSN
00221767
15506606
cat書誌ID
AA12067070
AA00699656
AA12530845
出版者
The American Association of Immunologists, Inc.
206
6
開始ページ
1204
終了ページ
1214
発行日
2021-01-27
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Tania Afrojの学位論文として提出され,学位審査・授与の対象となっている。
Originally published in The Journal of Immunology. Tania Afroj, Atsushi Mitsuhashi, Hirokazu Ogino, Atsuro Saijo, Kenji Otsuka, Hiroto Yoneda, Makoto Tobiume, Na Thi Nguyen, Hisatsugu Goto, Kazuya Koyama, Masamichi Sugimoto, Osamu Kondoh, Hiroshi Nokihara and Yasuhiko Nishioka. 2021. Blockade of PD-1/PD-L1 Pathway Enhances the Antigen-Presenting Capacity of Fibrocytes. J. Immunol. Vol.206(6) pp1204-1214.
権利情報
Copyright © 2021 by The American Association of Immunologists, Inc.
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3488号
学位記番号
甲医第1492号
学位授与年月日
2021-03-17
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院