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Cancer-associated oxidoreductase ERO1-α promotes immune escape through up-regulation of PD-L1 in human breast cancerCancer-associated oxidoreductase ERO1-α promotes immune escape through up-regulation of PD-L1 in human breast cancer |
"/Tanaka, Tsutomu/"Tanaka, Tsutomu ,
"/Kutomi, Goro/"Kutomi, Goro ,
"/Kajiwara, Toshimitsu/"Kajiwara, Toshimitsu ,
"/Kukita, Kazuharu/"Kukita, Kazuharu ,
"/Kochin, Vitaly/"Kochin, Vitaly ,
"/Kanaseki, Takayuki/"Kanaseki, Takayuki ,
"/Tsukahara, Tomohide/"Tsukahara, Tomohide ,
"/Hirohashi, Yoshihiko(1000030516901)/"Hirohashi, Yoshihiko 
,
"/Torigoe, Toshihiko/"Torigoe, Toshihiko ,
"/Okamoto, Yoshiharu/"Okamoto, Yoshiharu ,
"/Hirata, Koichi/"Hirata, Koichi ,
"/Sato, Noriyuki(1000050158937)/"Sato, Noriyuki ,
"/Tamura, Yasuaki(1000080322329)/"Tamura, Yasuaki
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15
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, pp.24706
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24718 , 2017-04 , Impact Journals
ISSN:1949-2553
Description
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.
Full-Text
https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/65818/1/14960-251309-3-PB.pdf
