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Journal of equine veterinary science2020; 97; 103338; doi: 10.1016/j.jevs.2020.103338

Immunohistochemical Analysis of Programmed Death-Ligand 1 Expression in Equine Sarcoids.

Abstract: The aim of the study was to assess the expression of the immune checkpoint inhibitor programmed death-ligand 1 (PD-L1) in equine sarcoids (ES). Programmed death-ligand 1 is expressed by various cancer cells to block T cell-mediated elimination of tumor cells. Antibodies targeting human PD-L1 were tested by immunohistochemistry for their cross-reactivity with equine PD-L1 using formalin-fixed, paraffin-embedded tissues. Our results do not support an important role of PD-L1-mediated immune evasion in ES disease and hence do not offer a rationale for anti-PD-1/PD-L1-based immunotherapy against ES.
Publication Date: 2020-12-03 PubMed ID: 33478763DOI: 10.1016/j.jevs.2020.103338Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research aimed to examine the existence of a specific immune system inhibitor, PD-L1, within equine sarcoids (ES) – a common skin tumor in horses. However, the study concluded that this immune inhibitor had no significant role in ES and therefore does not contribute to developing PD-1/PD-L1-focused immunotherapy for this condition.

Objective of the Study

  • The main goal of this research was to analyze the expression of PD-L1, an immune checkpoint inhibitor in equine sarcoids (ES). Equine sarcoids are frequent skin tumors found in horses.

PD-L1 and Its Role in Cancer

  • The programmed death-ligand 1 (PD-L1) is an immune checkpoint inhibitor that is often expressed by various cancer cells. These cells use PD-L1 to block T cell-mediated elimination of tumor cells and avoid the immune response.
  • Over the years, PD-L1/PD-1 pathway blockade has emerged as an effective therapeutic strategy for various human malignancies, leading to the hypothesis that similar mechanisms might be functional in equine tumors.

Methodology of the Study

  • To validate this theory, the researchers tested antibodies specifically targeting human PD-L1 for their capacity to interact (cross-react) with PD-L1 in horses. The testing was performed via immunohistochemistry, a method used to visually localize specific antigens in tissues, using formalin-fixed, paraffin-embedded tissues.

Results and their Implications

  • Despite their hypothesis, the research failed to support the substantial role of PD-L1-mediated immune evasion in ES disease, thereby disputing the possibility of employing PD-L1 as a targeted treatment for equine sarcoids.
  • This conclusion implies that therapies based on PD-1/PD-L1 blockade, effective in certain types of human cancer, may not be applicable for ES. The absence of substantial PD-L1 expression in sarcoids makes it an unlikely target for immunotherapy in horses.

Cite This Article

APA
Benvegnen J, De Breuyn B, Gerber V, Rottenberg S, Koch C. (2020). Immunohistochemical Analysis of Programmed Death-Ligand 1 Expression in Equine Sarcoids. J Equine Vet Sci, 97, 103338. https://doi.org/10.1016/j.jevs.2020.103338

Publication

ISSN: 0737-0806
NlmUniqueID: 8216840
Country: United States
Language: English
Volume: 97
Pages: 103338
PII: S0737-0806(20)30429-9

Researcher Affiliations

Benvegnen, Jennifer
  • Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Swiss Institute of Equine Medicine (ISME), Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland. Electronic address: j.benvegnen@hotmail.com.
De Breuyn, Bettina
  • Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Gerber, Vinzenz
  • Swiss Institute of Equine Medicine (ISME), Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.
Rottenberg, Sven
  • Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Koch, Christoph
  • Swiss Institute of Equine Medicine (ISME), Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.

MeSH Terms

  • Animals
  • B7-H1 Antigen / genetics
  • Horse Diseases
  • Horses
  • Immunohistochemistry
  • Immunotherapy / veterinary
  • Neoplasms / veterinary

Citations

This article has been cited 4 times.
  1. Porcellato I, Mecocci S, Brachelente C, Cappelli K, Armando F, Tognoloni A, Chiaradia E, Stefanetti V, Mechelli L, Pepe M, Gialletti R, Passeri B, Ghelardi A, Razzuoli E. PD-L1/PD-1 and CTLA-4 Expression in Equine Penile Squamous Cell Carcinomas. Animals (Basel) 2021 Jul 16;11(7).
    doi: 10.3390/ani11072121pubmed: 34359249google scholar: lookup
  2. Pimenta J, Prada J, Pires I, Cotovio M. Programmed-cell death ligand 1 (PD-L1) expression in equine sarcoids and squamous cell carcinoma. Open Vet J 2024 Jun;14(6):1476-1482.
    doi: 10.5455/OVJ.2024.v14.i6.16pubmed: 39055760google scholar: lookup
  3. Fesmire CC, Peal B, Ruff J, Moyer E, McParland TJ, Derks K, O'Neil E, Emke C, Johnson B, Ghosh S, Petrella RA, DeWitt MR, Prange T, Fogle C, Sano MB. Investigation of integrated time nanosecond pulse irreversible electroporation against spontaneous equine melanoma. Front Vet Sci 2024;11:1232650.
    doi: 10.3389/fvets.2024.1232650pubmed: 38352036google scholar: lookup
  4. Pimenta J, Prada J, Pires I, Cotovio M. Programmed Cell Death-Ligand 1 (PD-L1) Immunohistochemical Expression in Equine Melanocytic Tumors. Animals (Basel) 2023 Dec 22;14(1).
    doi: 10.3390/ani14010048pubmed: 38200779google scholar: lookup