Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 27 May 2021 / Approved: 28 May 2021 / Online: 28 May 2021 (13:26:41 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Vet. Sci. 2021, 8, 120
DOI: 10.3390/vetsci8070120

Abstract

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 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 CHOP (n=12) or CHOP plus 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.

Keywords

Dog; diffuse large B-cell lymphoma; PD-1; PD-L1; RNAscope

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