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

Tanaka, Tsutomu; Kutomi, Goro; Kajiwara, Toshimitsu; Kukita, Kazuharu; Kochin, Vitaly; Kanaseki, Takayuki; Tsukahara, Tomohide; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Okamoto, Yoshiharu; Hirata, Koichi; Sato, Noriyuki; Tamura, Yasuaki

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

Tanaka, Tsutomu; Kutomi, Goro; Kajiwara, Toshimitsu et al.

Oncotarget, 2017, 8(15), 24706-24718

Permalink : https://hdl.handle.net/2115/65818

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アクセス権	open access
URI	https://hdl.handle.net/2115/65818
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 ; Kutomi, Goro ; Kajiwara, Toshimitsu ; Kukita, Kazuharu ; Kochin, Vitaly ; Kanaseki, Takayuki ; Tsukahara, Tomohide ; Hirohashi, Yoshihiko ; Torigoe, Toshihiko ; Okamoto, Yoshiharu ; Hirata, Koichi ; Sato, Noriyuki ; Tamura, Yasuaki
著者名 Tanaka, Tsutomu
著者名 Kutomi, Goro
著者名 Kajiwara, Toshimitsu
著者名 Kukita, Kazuharu
著者名 Kochin, Vitaly
著者名 Kanaseki, Takayuki
著者名 Tsukahara, Tomohide
e-Rad_Researcher 30516901 著者名 Hirohashi, Yoshihiko
著者名 Torigoe, Toshihiko
著者名 Okamoto, Yoshiharu
著者名 Hirata, Koichi
e-Rad_Researcher 50158937 著者名 Sato, Noriyuki
e-Rad_Researcher 80322329 著者名 Tamura, Yasuaki
言語	英語
キーワード	ERO1-alpha
	PD-L1
	disulfide bond
	triple negative breast cancer
	oxidoreductase
発行日	2017-04
出版者	Impact Journals
収録物名	Oncotarget
巻(号)	8(15)
ページ	24706-24718
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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 3.0 Unported
PISSN	1949-2553
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.18632/oncotarget.14960