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Cancer-associated oxidoreductase ERO1-α promotes immune escape through up-regulation of PD-L1 in human breast cancer


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タイトル: Cancer-associated oxidoreductase ERO1-α promotes immune escape through up-regulation of PD-L1 in human breast cancer
著者: Tanaka, Tsutomu 著作を一覧する
Kutomi, Goro 著作を一覧する
Kajiwara, Toshimitsu 著作を一覧する
Kukita, Kazuharu 著作を一覧する
Kochin, Vitaly 著作を一覧する
Kanaseki, Takayuki 著作を一覧する
Tsukahara, Tomohide 著作を一覧する
Hirohashi, Yoshihiko 著作を一覧する
Torigoe, Toshihiko 著作を一覧する
Okamoto, Yoshiharu 著作を一覧する
Hirata, Koichi 著作を一覧する
Sato, Noriyuki 著作を一覧する
Tamura, Yasuaki 著作を一覧する
キーワード: ERO1-alpha
disulfide bond
triple negative breast cancer
発行日: 2017年 4月
出版者: Impact Journals
誌名: Oncotarget
巻: 8
号: 15
開始ページ: 24706
終了ページ: 24718
出版社 DOI: 10.18632/oncotarget.14960
抄録: Many human cancers have been reported to have enhanced expression of the immune checkpoint molecule programmed death-ligand 1 (PD-L1), which binds to programmed cell death-1 (PD-1) expressed on immune cells. PD-L1/PD-1 plays a role in inhibition of antitumor immunity by inducing T cell apoptosis and tolerance. Thus, it is crucial to elucidate mechanisms of PD-L1 expression on cancer cells. ERO1-alpha is an oxidase located in the endoplasmic reticulum. It is overexpressed in a variety of tumor types and it plays a role in disulfide bond formation in collaboration with PDI. Here, we investigated the influence of ERO1-alpha on expression of PD-L1 and immune escape. We demonstrated that ERO1-alpha augmented the expression of PD-L1 via facilitation of oxidative protein folding within PD-L1. In addition, we showed that overexpression of ERO1-alpha increased HIF-1 alpha protein expression, resulting in an increase of PD-L1 mRNA as well as protein. In clinical cases, we observed that the expression of ERO1-alpha in triple negative breast cancer was related to the expression of PD-L1. Moreover, apoptosis of Jurkat leukemia T cells, which express PD-1, induced by tumor PD-L1 was inhibited when ERO1-alpha was depleted. The results suggest that targeting ERO1-alpha in tumor cells can be a novel approach for cancer immunotherapy. Therefore, the role of ERO1-alpha in tumor-mediated immunosuppression should be further explored.
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 田村 保明


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