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Home / Equine Research Bank / PLoS One / PD-L1 expression in equine malignant melanoma and functional...
PloS one2020; 15(11); e0234218; doi: 10.1371/journal.pone.0234218

PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade.

Abstract: 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.
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Publication Date: 2020-11-20 PubMed ID: 33216754PubMed Central: PMC7678989DOI: 10.1371/journal.pone.0234218Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates the role of the PD-1/PD-L1 pathway in chronic equine diseases, including cancers such as equine malignant melanoma. The study used anti-bovine PD-L1 mAbs to examine the effects of PD-L1 blockade in equine immune cells, showing its potential use in immunotherapy.

Introduction and Background

  • The article begins by discussing the inhibitory role of Programmed death-1 (PD-1), an immunoinhibitory receptor expressed on lymphocytes. Specifically, when PD-1 interacts with PD-ligand 1 (PD-L1), it impairs several immune functions of T cells, such as proliferation, cytokine production and cytotoxicity.
  • Previous studies by the authors highlighted the association of the PD-1/PD-L1 pathway with T-cell exhaustion and disease progression in bovine chronic infections and canine tumors. They demonstrated that antibodies blocking PD-1/PD-L1 could restore T-cell functions and had potential use in immunotherapy.
  • Despite their findings, they noted that the immunological role of the PD-1/PD-L1 pathway in chronic equine diseases was unclear. This paper aimed to investigate this aspect.

Research Methodology

  • The study started with the identification of cDNA sequences of equine PD-1 and PD-L1.
  • They then used the anti-bovine PD-L1 monoclonal antibodies against EqPD-L1 in in vitro assays to investigate the role of PD-L1.
  • The expression of PD-L1 was also evaluated in tumor tissues of equine malignant melanoma using immunohistochemistry.
  • An assessment of the effects of PD-L1 blockade on cytokine production in equine immune cells was performed through a cultivation assay.

Findings and Conclusion

  • The research revealed that the amino acid sequences of EqPD-1 and EqPD-L1 have significant identity and similarity with non-primate species.
  • Two clones of the anti-bovine PD-L1 mAbs recognized EqPD-L1, and one of them blocked the binding of equine PD-1/PD-L1.
  • PD-L1 expression was confirmed in EMM tumor tissues.
  • PD-L1 blockade enhanced the production of Th1 cytokines in equine immune cells as revealed in the cultivation assay.
  • The study concluded that the anti-PD-L1 mAbs could be useful for analyzing the equine PD-1/PD-L1 pathway. The discovered knowledge may lead to an application of PD-L1 blockade as an immunotherapy for chronic equine diseases.

Cite This Article

APA
Ganbaatar O, Konnai S, Okagawa T, Nojima Y, Maekawa N, Minato E, Kobayashi A, Ando R, Sasaki N, Miyakoshi D, Ichii O, Kato Y, Suzuki Y, Murata S, Ohashi K. (2020). PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade. PLoS One, 15(11), e0234218. https://doi.org/10.1371/journal.pone.0234218

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 15
Issue: 11
Pages: e0234218
PII: e0234218

Researcher Affiliations

Ganbaatar, Otgontuya
  • Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Konnai, Satoru
  • Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
  • Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Okagawa, Tomohiro
  • Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Nojima, Yutaro
  • Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Maekawa, Naoya
  • Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Minato, Erina
  • Department of Veterinary Clinical Medicine, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Kobayashi, Atsushi
  • Department of Veterinary Clinical Medicine, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Ando, Ryo
  • Laboratory of Veterinary Pathology, School of Veterinary Medicine, Kitasato University, Towada, Japan.
Sasaki, Nobuya
  • Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, Towada, Japan.
Miyakoshi, Daisuke
  • Mitsuishi Animal Medical Center, NOSAI Minami, Shinhidaka, Japan.
Ichii, Osamu
  • Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Kato, Yukinari
  • Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan.
Suzuki, Yasuhiko
  • Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
  • Division of Bioresources, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Murata, Shiro
  • Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
  • Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Ohashi, Kazuhiko
  • Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
  • Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

MeSH Terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • Horses
  • Immunotherapy / methods
  • Melanoma / drug therapy
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma / veterinary
  • Sequence Homology

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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Citations

This article has been cited 14 times.
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