Equine Penile Squamous Cell Carcinomas as a Model for Human Disease: A Preliminary Investigation on Tumor Immune Microenvironment.
Abstract: Penile squamous cell carcinomas (SCCs) are common tumors in older horses, with poor prognosis mostly due to local invasion and recurrence. These tumors are thought to be mainly caused by papillomavirus type 2 (EcPV-2). The aim of this study is to characterize the tumor immune environment (TIME) in equine penile tumors. Equine penile epithelial tumors (17 epSCCs; 2 carcinomas , CIS; 1 papilloma, P) were retrospectively selected; immune infiltrate was assessed by histology and immunohistochemistry; RT-qPCR tested the expression of selected chemokines and EcPV-2 DNA and RNA. The results confirmed EcPV-2-L1 DNA in 18/20 (90%) samples. expression was instead retrieved in 13/20 cases (65%). The samples showed an increased infiltration of CD3lymphocytes, macrophages (MAC387; IBA1), plasma cells (MUM1), and FoxP3lymphocytes in the intra/peritumoral stroma when compared to extratumoral tissues ( < 0.05). Only MAC387neutrophils were increased in EcPV-2 viral load samples ( < 0.05). / was differentially expressed in EcPV and EcPV groups ( = 0.007). A significant decrease of and expression was highlighted in -positive samples ( < 0.05). IBA1 and CD20 were intratumorally increased in cases where IL-10 was expressed ( < 0.005). EpSCCs may represent a good spontaneous model for the human counterpart. Further prospective studies are needed in order to confirm these preliminary results.
Publication Date: 2020-10-27 PubMed ID: 33121116PubMed Central: PMC7693514DOI: 10.3390/cells9112364Google 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.
This research investigates the immune environment within penile squamous cell carcinomas, a type of tumor common in older horses, as a model for similar cancers in humans. Their aim is to understand the role of certain chemokines and the EcPV-2 virus in these tumors.
Objectives and Methodology
- The main objective of this study is to understand what goes on in the immune environment within equine penile squamous cell carcinomas, with the intent to use this knowledge to help treat the human variant of the disease.
- A total of 20 equine penile epithelial tumors were selected for the study. Using techniques such as histology and immunohistochemistry, the researchers analyzed the infiltration of immune response cells, like lymphocytes and macrophages, within the tumors.
- The researchers also used RT-qPCR, an advanced gene expression testing method, to find the presence and expression of EcPV-2 DNA and RNA, a papillomavirus considered the main cause of this type of cancer.
Findings
- The study found the presence of EcPV-2-L1 DNA in 90% of the samples and RNA expression in 65% of the cases. This strengthens the link between the papillomavirus and this cancer.
- They also observed an increased infiltration of various immune cells, like CD3 lymphocytes, macrophages, and plasma cells, in the intra and peritumoral stroma (tissue surrounding the tumor). This was in comparison to tissues that were not directly adjacent to the tumor.
- Furthermore, there was increased presence of MAC387 neutrophils, a type of immune response cell, in samples with high EcPV-2 viral load.
- The expression of certain chemokines, immune mediators, was found to be less in samples that were positive for EcPV-2.
- Another finding was that the presence of IBA1 and CD20, markers linked to particular immune cells, was increased in cases where IL-10, an immune suppression molecule, was expressed.
Implications and Future Directions
- The results from the study propose that equine squamous cell carcinomas could serve as a suitable model to study the human counterpart of the disease. This can help further our understanding and potentially lead to the development of targeted treatments.
- Although this is a preliminary study, the results provide a foundation for future exploration in this area of research. The authors acknowledge the need for more investigations to confirm these results.
Cite This Article
APA
Porcellato I, Mecocci S, Mechelli L, Cappelli K, Brachelente C, Pepe M, Orlandi M, Gialletti R, Passeri B, Ferrari A, Modesto P, Ghelardi A, Razzuoli E.
(2020).
Equine Penile Squamous Cell Carcinomas as a Model for Human Disease: A Preliminary Investigation on Tumor Immune Microenvironment.
Cells, 9(11), 2364.
https://doi.org/10.3390/cells9112364 Publication
Researcher Affiliations
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
- Centro di Ricerca sul Cavallo Sportivo, University of Perugia, 06126 Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
- Centro di Ricerca sul Cavallo Sportivo, University of Perugia, 06126 Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
- Centro di Ricerca sul Cavallo Sportivo, University of Perugia, 06126 Perugia, Italy.
- Department of Veterinary Science, University of Parma, 43126 Parma, Italy.
- Zooprophylactic Institute of Piemonte, Liguria and Valle d'Aosta, 16129 Genova, Italy.
- Zooprophylactic Institute of Piemonte, Liguria and Valle d'Aosta, 16129 Genova, Italy.
- Azienda Usl Toscana Nord-Ovest, UOC Ostetricia e Ginecologia, Ospedale Apuane, 54100 Massa, Italy.
- Zooprophylactic Institute of Piemonte, Liguria and Valle d'Aosta, 16129 Genova, Italy.
MeSH Terms
- Animals
- Biomarkers, Tumor / metabolism
- Carcinoma, Squamous Cell / immunology
- Carcinoma, Squamous Cell / pathology
- Carcinoma, Squamous Cell / veterinary
- Carcinoma, Squamous Cell / virology
- Cytokines / metabolism
- Disease Models, Animal
- Horses / immunology
- Humans
- Ki-67 Antigen / metabolism
- Male
- Papillomaviridae / physiology
- Penile Neoplasms / immunology
- Penile Neoplasms / pathology
- Penile Neoplasms / veterinary
- Penile Neoplasms / virology
- Tumor Microenvironment / immunology
- Viral Load
- Viral Proteins / metabolism
Grant Funding
- Grant 18C15 / funded by Italian Ministry of Health
Conflict of Interest Statement
The authors declare no conflict of interest.
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Citations
This article has been cited 6 times.- Cappelli K, Ciucis CG, Mecocci S, Nervo T, Crescio MI, Pepe M, Gialletti R, Pietrucci D, Migone LF, Turco S, Mechelli L, Passamonti F, Drago C, Donato GG, Varello K, Modesto P, Chillemi G, Ghelardi A, Razzuoli E. Detection of Equus Caballus Papillomavirus Type-2 in Asymptomatic Italian Horses. Viruses 2022 Jul 31;14(8).
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- 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).
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