| Title: | Cancer-associated oxidoreductase ERO1-α promotes immune escape through up-regulation of PD-L1 in human breast cancer |
| Authors: | Tanaka, Tsutomu Browse this author |
| Kutomi, Goro Browse this author |
| Kajiwara, Toshimitsu Browse this author |
| Kukita, Kazuharu Browse this author |
| Kochin, Vitaly Browse this author |
| Kanaseki, Takayuki Browse this author |
| Tsukahara, Tomohide Browse this author |
| Hirohashi, Yoshihiko Browse this author →KAKEN DB |
| Torigoe, Toshihiko Browse this author |
| Okamoto, Yoshiharu Browse this author |
| Hirata, Koichi Browse this author |
| Sato, Noriyuki Browse this author →KAKEN DB |
| Tamura, Yasuaki Browse this author →KAKEN DB |
| Keywords: | ERO1-alpha |
| PD-L1 |
| disulfide bond |
| triple negative breast cancer |
| oxidoreductase |
| Issue Date: | Apr-2017 |
| Publisher: | Impact Journals |
| Journal Title: | Oncotarget |
| Volume: | 8 |
| Issue: | 15 |
| Start Page: | 24706 |
| End Page: | 24718 |
| Publisher DOI: | 10.18632/oncotarget.14960 |
| Abstract: | 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. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/65818 |
| Appears in Collections: | 産学・地域協働推進機構 (Institute for the Promotion of Business-Regional Collaboration) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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