PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade.
Programmed death-1 (PD-1) is an immunoinhibitory receptor expressed on lymphocytes. Interaction of PD-1 with its ligand PD-ligand 1 (PD-L1) delivers inhibitory signals and impairs proliferation, cytokine production, and cytotoxicity of T cells. In our previous studies, we have developed anti-bovine...
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doaj-af45bb119142484c9b3fe705289e8a4d2021-03-04T12:26:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-011511e023421810.1371/journal.pone.0234218PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade.Otgontuya GanbaatarSatoru KonnaiTomohiro OkagawaYutaro NojimaNaoya MaekawaErina MinatoAtsushi KobayashiRyo AndoNobuya SasakiDaisuke MiyakoshiOsamu IchiiYukinari KatoYasuhiko SuzukiShiro MurataKazuhiko OhashiProgrammed death-1 (PD-1) is an immunoinhibitory receptor expressed on lymphocytes. Interaction of PD-1 with its ligand PD-ligand 1 (PD-L1) delivers inhibitory signals and impairs proliferation, cytokine production, and cytotoxicity of T cells. In our previous studies, we have developed anti-bovine PD-L1 monoclonal antibodies (mAbs) and reported that the PD-1/PD-L1 pathway was closely associated with T-cell exhaustion and disease progression in bovine chronic infections and canine tumors. Furthermore, we found that blocking antibodies that target PD-1 and PD-L1 restore T-cell functions and could be used in immunotherapy in cattle and dogs. However, the immunological role of the PD-1/PD-L1 pathway for chronic equine diseases, including tumors, remains unclear. In this study, we identified cDNA sequences of equine PD-1 (EqPD-1) and PD-L1 (EqPD-L1) and investigated the role of anti-bovine PD-L1 mAbs against EqPD-L1 using in vitro assays. In addition, we evaluated the expression of PD-L1 in tumor tissues of equine malignant melanoma (EMM). The amino acid sequences of EqPD-1 and EqPD-L1 share a considerable identity and similarity with homologs from non-primate species. Two clones of the anti-bovine PD-L1 mAbs recognized EqPD-L1 in flow cytometry, and one of these cross-reactive mAbs blocked the binding of equine PD-1/PD-L1. Of note, immunohistochemistry confirmed the PD-L1 expression in EMM tumor tissues. A cultivation assay revealed that PD-L1 blockade enhanced the production of Th1 cytokines in equine immune cells. These findings showed that our anti-PD-L1 mAbs would be useful for analyzing the equine PD-1/PD-L1 pathway. Further research is warranted to discover the immunological role of PD-1/PD-L1 in chronic equine diseases and elucidate a future application in immunotherapy for horses.https://doi.org/10.1371/journal.pone.0234218 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Otgontuya Ganbaatar Satoru Konnai Tomohiro Okagawa Yutaro Nojima Naoya Maekawa Erina Minato Atsushi Kobayashi Ryo Ando Nobuya Sasaki Daisuke Miyakoshi Osamu Ichii Yukinari Kato Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi |
spellingShingle |
Otgontuya Ganbaatar Satoru Konnai Tomohiro Okagawa Yutaro Nojima Naoya Maekawa Erina Minato Atsushi Kobayashi Ryo Ando Nobuya Sasaki Daisuke Miyakoshi Osamu Ichii Yukinari Kato Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade. PLoS ONE |
author_facet |
Otgontuya Ganbaatar Satoru Konnai Tomohiro Okagawa Yutaro Nojima Naoya Maekawa Erina Minato Atsushi Kobayashi Ryo Ando Nobuya Sasaki Daisuke Miyakoshi Osamu Ichii Yukinari Kato Yasuhiko Suzuki Shiro Murata Kazuhiko Ohashi |
author_sort |
Otgontuya Ganbaatar |
title |
PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade. |
title_short |
PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade. |
title_full |
PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade. |
title_fullStr |
PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade. |
title_full_unstemmed |
PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade. |
title_sort |
pd-l1 expression in equine malignant melanoma and functional effects of pd-l1 blockade. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
Programmed death-1 (PD-1) is an immunoinhibitory receptor expressed on lymphocytes. Interaction of PD-1 with its ligand PD-ligand 1 (PD-L1) delivers inhibitory signals and impairs proliferation, cytokine production, and cytotoxicity of T cells. In our previous studies, we have developed anti-bovine PD-L1 monoclonal antibodies (mAbs) and reported that the PD-1/PD-L1 pathway was closely associated with T-cell exhaustion and disease progression in bovine chronic infections and canine tumors. Furthermore, we found that blocking antibodies that target PD-1 and PD-L1 restore T-cell functions and could be used in immunotherapy in cattle and dogs. However, the immunological role of the PD-1/PD-L1 pathway for chronic equine diseases, including tumors, remains unclear. In this study, we identified cDNA sequences of equine PD-1 (EqPD-1) and PD-L1 (EqPD-L1) and investigated the role of anti-bovine PD-L1 mAbs against EqPD-L1 using in vitro assays. In addition, we evaluated the expression of PD-L1 in tumor tissues of equine malignant melanoma (EMM). The amino acid sequences of EqPD-1 and EqPD-L1 share a considerable identity and similarity with homologs from non-primate species. Two clones of the anti-bovine PD-L1 mAbs recognized EqPD-L1 in flow cytometry, and one of these cross-reactive mAbs blocked the binding of equine PD-1/PD-L1. Of note, immunohistochemistry confirmed the PD-L1 expression in EMM tumor tissues. A cultivation assay revealed that PD-L1 blockade enhanced the production of Th1 cytokines in equine immune cells. These findings showed that our anti-PD-L1 mAbs would be useful for analyzing the equine PD-1/PD-L1 pathway. Further research is warranted to discover the immunological role of PD-1/PD-L1 in chronic equine diseases and elucidate a future application in immunotherapy for horses. |
url |
https://doi.org/10.1371/journal.pone.0234218 |
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