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Article

Prognostic Value of PD-L1, PD-1 and CD8A in Canine Diffuse Large B-Cell Lymphoma Detected by RNAscope

1
Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy
2
Department of Medical Veterinary Science, University of Bologna, 40064 Ozzano dell’Emilia, Italy
3
Department of Veterinary Medicine, University of Milan, 26900 Lodi, Italy
4
Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), 35020 Legnaro, Italy
*
Author to whom correspondence should be addressed.
Academic Editors: Massimo Vignoli and Arianna Miglio
Received: 27 May 2021 / Revised: 24 June 2021 / Accepted: 28 June 2021 / Published: 29 June 2021
(This article belongs to the Special Issue Lymphoma in Animals)
Immune checkpoints are a set of molecules dysregulated in several human and canine cancers and aberrations of the PD-1/PD-L1 axis are often correlated with a worse prognosis. To gain an insight into the role of immune checkpoints in canine diffuse large B-cell lymphoma (cDLBCL), we investigated PD-L1, PD-1 and CD8A expression by RNAscope. Results were correlated with several clinico-pathological features, including treatment, Ki67 index and outcome. A total of 33 dogs treated with chemotherapy (n = 12) or chemoimmunotherapy with APAVAC (n = 21) were included. PD-L1 signal was diffusely distributed among neoplastic cells, whereas PD-1 and CD8A were localized in tumor infiltrating lymphocytes. However, PD-1 mRNA was also retrieved in tumor cells. An association between PD-L1 and PD-1 scores was identified and a higher risk of relapse and lymphoma-related death was found in dogs treated with chemotherapy alone and dogs with higher PD-L1 and PD-1 scores. The correlation between PD-L1 and PD-1 is in line with the mechanism of immune checkpoints in cancers, where neoplastic cells overexpress PD-L1 that, in turn, binds PD-1 receptors in activated TIL. We also found that Ki67 index was significantly increased in dogs with the highest PD-L1 and PD-1 scores, indirectly suggesting a role in promoting tumor proliferation. Finally, even if the biological consequence of PD-1+ tumor cells is unknown, our findings suggest that PD-1 intrinsic expression in cDLBCL might contribute to tumor growth escaping adaptive immunity. View Full-Text
Keywords: dog; diffuse large B-cell lymphoma; PD-1; PD-L1; RNAscope dog; diffuse large B-cell lymphoma; PD-1; PD-L1; RNAscope
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MDPI and ACS Style

Aresu, L.; Marconato, L.; Martini, V.; Fanelli, A.; Licenziato, L.; Foiani, G.; Melchiotti, E.; Nicoletti, A.; Vascellari, M. Prognostic Value of PD-L1, PD-1 and CD8A in Canine Diffuse Large B-Cell Lymphoma Detected by RNAscope. Vet. Sci. 2021, 8, 120. https://0-doi-org.brum.beds.ac.uk/10.3390/vetsci8070120

AMA Style

Aresu L, Marconato L, Martini V, Fanelli A, Licenziato L, Foiani G, Melchiotti E, Nicoletti A, Vascellari M. Prognostic Value of PD-L1, PD-1 and CD8A in Canine Diffuse Large B-Cell Lymphoma Detected by RNAscope. Veterinary Sciences. 2021; 8(7):120. https://0-doi-org.brum.beds.ac.uk/10.3390/vetsci8070120

Chicago/Turabian Style

Aresu, Luca, Laura Marconato, Valeria Martini, Antonella Fanelli, Luca Licenziato, Greta Foiani, Erica Melchiotti, Arturo Nicoletti, and Marta Vascellari. 2021. "Prognostic Value of PD-L1, PD-1 and CD8A in Canine Diffuse Large B-Cell Lymphoma Detected by RNAscope" Veterinary Sciences 8, no. 7: 120. https://0-doi-org.brum.beds.ac.uk/10.3390/vetsci8070120

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