PD-L1/PD-1 and CTLA-4 Expression in Equine Penile Squamous Cell Carcinomas

Porcellato, Ilaria; Mecocci, Samanta; Brachelente, Chiara; Cappelli, Katia; Armando, Federico; Tognoloni, Alessia; Chiaradia, Elisabetta; Stefanetti, Valentina; Mechelli, Luca; Pepe, Marco; Gialletti, Rodolfo; Passeri, Benedetta; Ghelardi, Alessandro; Razzuoli, Elisabetta

doi:10.3390/ani11072121

Cited by 8 publications

(9 citation statements)

References 42 publications

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“…EcPV2 detection was assessed in 100 ng of DNA sample. In particular, L1, E2, E6, and E7 amplification by the real-time PCR assay was performed applying previously described protocols [10,18,19] and using the amplification of the equine beta-2-microglobulin (B2M) gene [10,20] as the control for DNA integrity (primer and probes sequences are reported in Table 1). Moreover, internal controls (block blanks, extraction blanks, and positive controls) were used for each analytical session.…”

Section: Ecpv2 Dna Real-time Pcrmentioning

confidence: 99%

Detection of Equus Caballus Papillomavirus Type-2 in Asymptomatic Italian Horses

Cappelli

Ciucis

Mecocci

et al. 2022

Viruses

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Equine Papillomavirus 2 (EcPV2) is responsible for squamous cell carcinomas (eSCCs) of external genitalia of both male and female horses. However, few studies report the EcPV2 prevalence among healthy horses. Currently, the lack of these data does not permit identifying at-risk populations and, thus, developing screening protocols aimed at the early detection of the infection, as for humans. The aim of our study was to estimate the genoprevalence of EcPV2 in clinically healthy horses in Italy and to evaluate their innate immune response. For this purpose, penile and vulvar swabs of 234 healthy horses were collected through sampling with sterile cytobrushes. Nucleic acids were isolated and EcPV2-L1 presence (DNA) and gene expression (RNA) were checked by RT-qPCR. Our results showed EcPV2-L1 DNA presence in 30.3% of the samples and L1 expression in 48% of the positive samples. No statistically significant differences were found in genoprevalence in relation to sex, age, and origin, while, concerning breeds, the Thoroughbred had the highest risk of infection. Concerning specifically the mares, 40.2% of them resulted in being positive for EcPV2; our findings show a major positivity in pluriparous (p = 0.0111) and mares subjected to natural reproduction (p = 0.0037). Moreover, samples expressing L1 showed an increased expression of IL1B (p = 0.0139) and IL12p40 (p = 0.0133) and a decreased expression of RANKL (p = 0.0229) and TGFB (p = 0.0177). This finding suggests the presence of an effective immune response, which could explain the low incidence of SCCs in positive horses, despite a high EcPV2 genoprevalence (30%).

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Section: Ecpv2 Dna Real-time Pcrmentioning

confidence: 99%

Detection of Equus Caballus Papillomavirus Type-2 in Asymptomatic Italian Horses

Cappelli

Ciucis

Mecocci

et al. 2022

Viruses

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“…Anti-bovine PD-L1 antibody shows cross-reactivity with porcine PD-L1 [ 67 ] and canine PD-L1 [ 68 ]. In addition, cross-reactive anti-human PD-1, PD-L1, or PD-L2 antibodies were used in canine [ 69 ], equine [ 70 ], and feline tissues [ 71 ].…”

Section: Beyond Humans and Micementioning

confidence: 99%

“…The examination of 20 equine penile squamous cell carcinomas revealed PD-L1 mRNA and protein in three cases and one case, respectively, whereas PD-1 expression was not detected [ 70 ].…”

Section: Beyond Humans and Micementioning

confidence: 99%

The PD-1/PD-L1 Pathway: A Perspective on Comparative Immuno-Oncology

Schöniger¹,

Jasani²

2022

Animals

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The programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway mainly attracted attention in immuno-oncology, leading to the development of immune checkpoint therapy. It has, however, much broader importance for tissue physiology and pathology. It mediates basic processes of immune tolerance and tissue homeostasis. In addition, it is involved in the pathogenesis of chronic infectious diseases, autoimmunity, and cancer. It is also an important paradigm for comparative pathology as well as the “one health one medicine” concept. The aim of this review is to provide an overview of novel research into the diverse facets of the PD-1/PD-L1 pathway and to give insights into its fine-tuning homeostatic role in a tissue-specific context. This review details early translational research from the discovery phase based on mice as animal models for understanding pathophysiological aspects in human tissues to more recent research extending the investigations to several animal species. The latter has the twofold goal of comparing this pathway between humans and different animal species and translating diagnostic tools and treatment options established for the use in human beings to animals and vice versa.

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“…Considering the existent evidence regarding the positive clinical effects of PD-1/PD-L1 blockade in the treatment of melanoma, it is pertinent to assess whether equine melanomas are potential candidates for this therapy. Although some articles have been published, according to the authors’ knowledge, the literature regarding PD-L1 expression in equine tumors is scarce and the sample dimension in the published articles is quite small, compromising the interpretation of the results [ 53 , 54 , 55 ].…”

Section: Introductionmentioning

confidence: 99%

Programmed Cell Death-Ligand 1 (PD-L1) Immunohistochemical Expression in Equine Melanocytic Tumors

Pimenta,

Prada,

Pires

et al. 2023

Animals

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Currently available treatments for equine melanocytic tumors have limitations, mainly due to mass localization and dimension, or the presence of metastases. Therefore, a search for new therapies is necessary. Programmed cell death-ligand 1 (PD-L1) is expressed by several tumors, blocking T cell-mediated elimination of the tumor cells by binding to programmed cell death protein 1 (PD-1). A novel therapeutic approach using PD-1/PD-L1 blockade in human melanoma resulted in tumor regression and prolonged tumor-free survival. This study aimed to evaluate the immunohistochemical expression of PD-L1 in equine melanocytic tumors. A total of 77 melanocytic tumors were classified as benign or malignant and evaluated by extension of labeling. A total of 59.7% of the tumors showed >50% of immunolabeled cells. Regarding malignant tumors, 24/38 tumors presented >50% of labeled cells, 13 tumors presented between 25–50% and one tumor presented <10%. Regarding benign tumors, 22/39 tumors presented >50% of labeled cells, nine tumors presented 25–50%, three tumors presented 10–25%, two tumors presented <10% and three tumors did not present expression. Our results suggest that PD-L1 blockade may be a potential target for immunotherapy in equine melanocytic tumors and that future clinical research trials into the clinical efficacy of the anti-PD-L1 antibody are necessary.

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PD-L1/PD-1 and CTLA-4 Expression in Equine Penile Squamous Cell Carcinomas

Cited by 8 publications

References 42 publications

Detection of Equus Caballus Papillomavirus Type-2 in Asymptomatic Italian Horses

Detection of Equus Caballus Papillomavirus Type-2 in Asymptomatic Italian Horses

The PD-1/PD-L1 Pathway: A Perspective on Comparative Immuno-Oncology

Programmed Cell Death-Ligand 1 (PD-L1) Immunohistochemical Expression in Equine Melanocytic Tumors

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