Cancer-associated oxidoreductase ERO1-α promotes immune escape through up-regulation of PD-L1 in human breast cancer
| Autor: | Yasuaki Tamura, Yoshiharu Okamoto, Koichi Hirata, Toshimitsu Kajiwara, Noriyuki Sato, Yoshihiko Hirohashi, Toshihiko Torigoe, Tsutomu Tanaka, Vitaly Kochin, Takayuki Kanaseki, Goro Kutomi, Tomohide Tsukahara, Kazuharu Kukita |
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| Rok vydání: | 2017 |
| Předmět: |
PD-L1
0301 basic medicine Protein Folding Leukemia T-Cell medicine.medical_treatment Apoptosis Breast Neoplasms Triple Negative Breast Neoplasms Transfection Jurkat cells B7-H1 Antigen Interferon-gamma Jurkat Cells 03 medical and health sciences Immune system Cancer immunotherapy Cell Line Tumor medicine Humans ERO1-alpha oxidoreductase Triple-negative breast cancer ERO1-α Membrane Glycoproteins biology business.industry Cancer medicine.disease Immune checkpoint Up-Regulation 030104 developmental biology Oncology triple negative breast cancer Immunology Cancer cell Cancer research biology.protein disulfide bond Female Tumor Escape Oxidoreductases business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.14960 |
| Popis: | // Tsutomu Tanaka 1, 2 , Goro Kutomi 3 , Toshimitsu Kajiwara 1 , Kazuharu Kukita 3 , Vitaly Kochin 1 , Takayuki Kanaseki 1 , Tomohide Tsukahara 1 , Yoshihiko Hirohashi 1 , Toshihiko Torigoe 1 , Yoshiharu Okamoto 4 , Koichi Hirata 3 , Noriyuki Sato 1 , Yasuaki Tamura 5 1 Department of Pathology, Sapporo Medical University, Sapporo, Japan 2 Department of Clinical Veterinary Medicine, The United Graduate School of Veterinary Sciences, Yamaguchi University, Yamaguchi, Japan 3 Department of Surgery, Sapporo Medical University, Sapporo, Japan 4 Joint Department of Veterinary Medicine, Tottori University, Tottori, Japan 5 Department of Molecular Therapeutics, Institute for the Business-Regional Collaboration, Center for Food & Medical Innovation, Hokkaido University, Sapporo, Japan Correspondence to: Yasuaki Tamura, email: ytamura3566@gmail.com Keywords: ERO1-α, PD-L1, disulfide bond, triple negative breast cancer, oxidoreductase Received: April 07, 2016 Accepted: January 03, 2017 Published: February 01, 2017 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-α 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-α on expression of PD-L1 and immune escape. We demonstrated that ERO1-α augmented the expression of PD-L1 via facilitation of oxidative protein folding within PD-L1. In addition, we showed that overexpression of ERO1-α increased HIF-1α protein expression, resulting in an increase of PD-L1 mRNA as well as protein. In clinical cases, we observed that the expression of ERO1-α 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-α was depleted. The results suggest that targeting ERO1-α in tumor cells can be a novel approach for cancer immunotherapy. Therefore, the role of ERO1-α in tumor-mediated immunosuppression should be further explored. |
| Databáze: | OpenAIRE |
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